The Outcomes of Vitrified Oocytes Accumulation for Managing Diminished Ovarian Reserve: A retrospective cohort study

The Outcomes of Vitrified Oocytes Accumulation for Managing Diminished Ovarian Reserve: A retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Outcomes of Vitrified Oocytes Accumulation for Managing Diminished Ovarian Reserve: A retrospective cohort study Kuan-Sheng Lee, Ming-Huei Lin, Yuh-Ming Hwu, Jia-Hwa Yang, Robert Kuo-Kuang Lee This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1482330/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Vitrified M-II oocytes accumulation strategy for later simultaneous insemination has been used for managing POR. Our study aimed to determine whether simulation insemination of vitrified oocytes accumulation strategy improves live birth rate (LBR) for managing diminished ovarian reserve (DOR). Methods: Retrospective study included 440 women with DOR fulfilling Poseidon classification groups 3 and 4, defined as presence of serum anti-Müllerian hormone (AMH) hormone level <1.2 ng/ml or antral follicle count (AFC) <5, from January 1, 2014 to December 31, 2019 in a single department. Patients underwent accumulation of vitrified oocytes (DOR-Accu) and embryo transfer (ET) or controlled ovarian stimulation (COS) using fresh oocytes (DOR-fresh) and ET. Primary outcomes were LBR per ET and cumulative LBR (CLBR) per intention to treat (ITT). Secondary outcomes were clinical pregnancy rate (CPR) and miscarriage rate (MR). Results: 211 patients underwent simultaneous insemination of vitrified oocytes accumulation and ET in DOR-Accu group (maternal age: 39.29 ± 4.23 y, AMH: 0.54 ± 0.35 ng/ml), and 229 patients underwent COS and ET in DOR-fresh group (maternal age: 38.07 ± 3.77 y, AMH: 0.72 ± 0.32 ng/ml). CPR in DOR-Accu group were similar in DOR-fresh group (27.5% vs. 31.0%, p = 0.418). MR was statistically higher (41.4% vs. 14.1%, p = 0.001) while LBR per ET was statistically lower (15.2% vs. 26.2%, p < 0.001) in DOR-Accu group. There is no difference in CLBR per ITT between groups (20.4% vs. 27.5%, p = 0.081). Clinical outcomes were categorized in four groups with regard to patient’s age in secondary analysis. CPR, LBR per ET, and CLBR did not improved in DOR-Accu group. In group of 31 patients, accumulated vitrified metaphase II (M-II) oocytes reach total number ≥15, CPR improved among DOR-Accu group (48.4% vs. 31.0%, p = 0.054); however, higher MR (40.0% vs. 14.1%, p = 0.03) resulted similar LBR per ET (29.0% vs. 26.2%, p = 0.738). Conclusions: Vitrified oocytes accumulation for managing DOR did not improve LBR. Higher MR resulted in lower LBR. Vitrified oocytes accumulation strategy for managing DOR is not clinically practical. Trial registration: The study protocol was retrospectively registered and was approved by Institutional Review Board of Mackay Memorial Hospital (21MMHIS219e) on August 26, 2021 Diminished ovarian reserve (DOR) fresh oocyte vitrified oocytes accumulation live birth rate (LBR) Introduction Poor ovarian responders (POR) or DOR are encountered during infertility treatment, and poor prognosis during improves in vitro fertilization (IVF) treatment is ascribed with it [ 1 – 3 ]. Vitrified M-II oocytes accumulation strategy for later simultaneous insemination has been used for managing POR since two studies reported that it improved IVF outcome [ 4 , 5 ]. In patients with POR, current data came from vitrified oocytes accumulation were pooled together with fresh oocytes. It caused a difficulty in determining contribution of CPR and LBR from pooling together vitrified oocytes or fresh oocytes. We determined whether vitrified oocytes accumulation strategy from DOR women improves LBR in assisted reproduction technology (ART). Numerous randomized controlled trials and prospective and retrospective studies have shown that cryopreserved oocytes provide reproductive outcomes comparable to fresh oocytes use [ 6 – 21 ]. However, large cohort analysis has indicated overall lower reproductive outcomes using vitrified donor oocytes rather than using fresh donor oocytes [ 22 – 24 ]. The alterations have been found in gene expression and reduced mitochondrial DNA content in vitrified and thawed oocytes [ 25 – 27 ]. Despite of extensive literature examining cryopreserved oocyte quality clinical characteristics, there is still lacking data regarding whether ART outcomes of using vitrified and thawed oocytes from DOR women is comparable with using fresh oocytes from DOR women. Therefore, the study objective was to evaluate whether vitrified oocytes accumulation for later simultaneous insemination improve LBR to manage DOR. Materials And Methods Study Design A medical record review was performed for DOR woman who underwent COS and ET using vitrified oocytes accumulation for later simultaneous insemination or using fresh oocytes at Infertility Division of Mackay Memorial Hospital in Taipei City, Taiwan from January 1, 2014 to December 31, 2019. The patients were followed during treatment at our center for at least 1 year until either treatment discontinuation or 1 live infant delivery. The study protocol was approved by Institutional Review Board of Mackay Memorial Hospital (21MMHIS219e). Study Participants DOR was made in accordance with the Poseidon ( P atient- O riented S trategies E ncompassing I ndividualize D O ocyte N umber) classification groups 3 and 4 [28], defined as presence of low serum AMH hormone level (<1.2 ng/ml) or low AFC (<5) at time of ovarian stimulation initiation. All patients who met the criteria of Poseidon Groups 3 and 4 and had at least 1 embryo created intended to transfer during current cycle were included. Exclusion criteria were coexisting endocrine disorders (diabetes mellitus, untreated hyperprolactinemia, untreated thyroid dysfunction, congenital adrenal hyperplasia, and Cushing’s syndrome), untreated hydrosalpinx, and uterine anomaly confirmed either by hysterosalpingography or hysteroscopy. After applying the exclusion criteria, a total of 440 DOR women who underwent fresh ET were included for final analysis. The study group included 211 patients with vitrified M-II oocytes accumulation for later simultaneous insemination. This group was named “diminished ovarian reserve, accumulation of vitrified oocytes” (DOR-Accu). In this group, we used double stimulation in same ovarian cycle to maximize the oocytes number retrieved in a short time frame [29, 30]. After oocyte retrieval, all mature oocytes were vitrified and stored. Luteal phase ovarian stimulation following oocyte retrieval was performed based on number of remainder AFC. The decision about whether to stop oocytes accumulation was based on two factors as follows: (1) the vitrified M-II oocytes total number reaches 10–15 which was expected to maximize the LBR [31-33] and (2) the patient’s own decision. The control group included 229 DOR patients who underwent gonadotropin-releasing hormone (GnRH) agonist-flare protocol or GnRH antagonist protocol, whose fresh mature oocytes were inseminated and subsequent ET was named “diminished ovarian reserve, fresh oocytes” (DOR-fresh). Surplus embryos in both groups had been vitrified and transferred in their subsequent cycle until surplus embryos exhaust or patient gets at least 1 live infant delivery. Ovarian Stimulation Protocols People in the DOR-fresh group using GnRH antagonist or GnRH agonist-flare protocol. Patients using GnRH agonist-flare or GnRH antagonist protocol started 300–450 IU recombinant FSH (Gonal-F; Merck Serono) or follitropin β (Puregon ® ; Organon) either alone or in combination with human menopausal gonadotropin (Menopur; Ferring) on day 2–3 of menstrual cycle. Patients using mild stimulation received oral compound such as letrozole (Femara; Genepharm S.A) 5 mg/day prior to gonadotropin stimulation on day 2–6 of menstrual cycle and followed by stimulation with 150 IU/day subcutaneous gonadotropin (Gonal-F or human menopausal gonadotropin or Puregon) on day 7 of menstrual cycle. In the GnRH agonist protocol, pituitary flare up with 0.5 mg subcutaneous leuprolide acetate (Takeda Pharma GmbH, Stolberg, Germany) beginning on day 2 of menstrual cycle until trigger day. In GnRH antagonist protocol, 0.25 mg subcutaneous cetrorelix (Cetrotide; Merck Serono) was administered daily when follicles reached ≥ 14 mm in diameter until trigger day. The gonadotropin dosage was adjusted every 2–3 days in accordance with follicle growth. People in the DOR-Accu group using double stimulations in same menstrual cycle with gonadotropins and clomiphene or letrozole combination. In follicle phase stimulation, clomiphene citrate 150 mg/day or letrozole 7.5 mg/day were given on day 2–3 of menstrual cycle onward. Gonadotropin 150–450 IU/day was added later when 3 three follicles reached >10 mm in diameter and 0.25-mg subcutaneous cetrorelix (Cetrotide; Merck Serono) was administered in presence of 14-mm follicle until trigger day. Transvaginal ultrasound was performed after oocyte retrieval, and clomiphene citrate 150 mg/day or letrozole (7.5 mg/day) was given in presence of 1 AFC. Gonadotropin 150–450 IU/day was added when 3 three follicles reached 10 mm until trigger day. GnRH antagonist was administered as follicular phase. When leading follicle reached 18 mm in diameter, final oocyte maturation was triggered by combination of 250-μg recombinant hCG (Ovidrel; Merck Serono) and 0.2-mg triptorelin (Decapeptyl; Ferring). Oocyte retrievals were performed under transvaginal ultrasound guidance, 35 to 36 h post triggering. The oocytes from DOR-Accu group were vitrificated by 3-step gradient cryoprotectant loading process using Cryotec Vitrification Method® (REPROLIFE Inc. 2-5-3-9F Shinjuku, Tokyo, Japan). The oocytes were equilibrated for 12–15 mins in 0.3-ml equilibration solution. Then oocytes were washed in a 0.3-ml vitrification solution (VS) for 30–40 secs and replaced with new 0.3-ml VS for another 10–20 secs. In next step, oocytes were loaded on Cryotec seat with minimum (0.01–0.1μl) VS volume and immediately submerge Cryotec into liquid nitrogen directly and then cover with cap. All procedure was performed at room temperature (25°C–27°C) with media being prepared at least 1 h in advance. Firstly, warming procedure (REPROLIFE Inc. 2-5-3-9F Shinjuku, Tokyo, Japan) started with Cryotec removal from liquid nitrogen and its immersion in 1-ml warming solution (TS) for 1 min. Secondly, oocytes were transferred into 0.3-ml dilution solution for 3 minutes. Thirdly, oocytes were equilibrated in 0.3-ml washing solution (WS) for another 5 minutes and replaced with a new 0.3-ml WS for another 1 min. Finally, oocytes were incubated in culture media for 2 h at 37°C, 6.0% CO 2 , and 5% O 2 before intracytoplasmic sperm injection (ICSI). TS was placed in incubator at 37°C at least 3 h before use, and other two were prepared 1 h at room temperature (25°C–27°C) in advance. All warming procedure was also performed at room temperature. Insemination and Embryo Transfer Warmed oocytes were cultured for 3 h prior to ICSI. Fresh oocytes were denudated immediately following oocyte retrieval. In vitro insemination procedures were performed 38 to 39 h post triggering for fresh oocytes, with exceptions in male factor, which ICSI were performed instead. Assisted hatching was performed to improve embryo capacity to implant. Endometrial Preparation, Luteal Phase Support, and Pregnancy Con fi rmation In DOR-fresh group, patients received 50-mg progesterone on oocyte retrieval day. Then, plus 125-μg intramuscular injection recombinant hCG (Ovidrel; Merck Serono) every 3 days plus daily vaginal supplementation of 90-mg vaginal progesterone gel (Crinone 8%; Merck Serono) or oral 10-mg dydrogesterone (Duphaston ® ; Abbott Biologicals) every 8 h plus 2-mg oral estradiol (E2) valerate (Progynova; Synmosa Biopharma Corporation) every 8 h plus vaginal supplementation of 90-mg vaginal progesterone gel (Crinone 8%; Merck Serono) every 12 h started on day 1 after oocyte retrieval as following luteal phase support. In DOR-Accu group, endometrial preparation was started with oral estradiol (E2) valerate (Progynova; Synmosa Biopharma Corporation) 8mg daily on day 1–3 of menstrual cycle. After 7 days of oral estrogen supplementation, we started to perform ultrasound to measure endometrial thickness. If endometrium was thinner than 7 mm at day 8, we increased estrogen dose to 12 mg daily followed by a reevaluation with ultrasound on day 13 of estrogen supplementation. If endometrium had reached at least 7 mm, all vitrified oocytes were warmed and inseminated by ICSI. We continued oral estrogen 8 mg daily and started 90-mg vaginal progesterone gel (Crinone 8%; Merck Serono) every 12 h plus 10-mg oral dydrogesterone (Duphaston ® ; Abbott Biologicals) every 8 h since the inseminated oocytes day (day 0). If endometrium had reached 7 mm or more, oocytes thawing, endometrial preparation, and luteal phase support started on day 1 after thawing oocytes were done as mention before. After oocytes retrieval or oocytes thawing, serum β-hCG was measured 14 days later, or urine hCG was checked 16 days later. Serum β-hCG above 5 mIU/mL or urine hCG above 25 mIU/mL was considered to be a positive pregnancy. Luteal support was continued until 10th week of gestation. Primary and Secondary Outcomes The study’s primary outcomes were LBR per ET and CLBR per ITT. Secondry outcomes included oocyte survival rate, fertilization rate, mean number of embryos transferred, CPR per ET, implantation rate (IR), MR per pregnancy, mean number of surplus vitrified embryo, and CLBR per OPU. A subgroup analysis was conducted on cases reach total number ≥ 10 and ≥ 15 M-II oocytes. To control repeat ET confounding factor, we only include last cycle with ET for final analysis if patients underwent repeat IVF cycle or repeat vitrified oocytes accumulation for later simultaneous insemination. LBR was defined as number of delivery resulted in a live born neonate who reached 20-weekgestational age per ET. CLBR calculated live birth until either cryotransfers of all embryos or 1 live infant delivery fertilization was assessed 16–18 h after insemination by visualization of 2 pronuclei and 2 polar bodies. CPR was defined as presence of at least 1 gestational sac between 5 th and 6 th weeks of gestation in ultrasound per ET. IR was calculated by dividing total number of gestational sac detected by total number of transferred embryos. MR was defined as spontaneous loss of all intrauterine pregnancy prior to completed 20-week gestational age. For OPU number, we only count retrievals, at least 1 M-II oocytes was available for later insemination. Statistical Analysis Statistical analysis was performed with R software, version 3.3.1 (R Project for Statistical Computing, Vienna, Austria). Differences in demographics among two groups were assessed with Student’s t- test, chi-square, or Fisher’s test, and results for continuous variables were presented as mean standard deviation; whereas, categorical variables were expressed as percentages. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were calculated by logistic regression analysis with relevant significant variables adjustment to assess effect of age, strategy, AMH, number of embryos transferred, and ET day on clinical outcomes. The 95% CIs for differences between proportions were calculated for LBR. Statistical significance was defined at 95% level (P < 0.05). Results Table 1 showed mean age at ART start were older in DOR-Accu group (39.29y vs. 38.07y, p < 0.001), and mean AMH were lower in DOR-Accu group (0.54 ng/ml vs. 0.72 ng/ml, p < 0.001) than the DOR-fresh group. There is no difference in reason for ART between groups. In DOR-fresh group, total of 229 women obtained 809 mature oocytes, resulting in mean 3.53 M-II oocytes for insemination. The DOR-Accu group consisted of 211 patients who received 1,130 stimulation and oocyte retrieval cycles, resulting in mean 5.36 cycles per woman. A total number of 2,089 M-II oocytes were retrieved and vitrified. These oocytes were warmed, and 1,791 survival M-II oocytes (survival rate: 85.7%) were submitted to ICSI. Fertilization rates, CPR, and IR in the DOR-Accu group were similar to DOR-fresh group. Mean number of embryos transferred per cycle was more in DOR-Accu group (2.96 vs. 2.14, p < 0.001). MR was statistically higher (41.4% vs. 14.1%, p < 0.001) and LBR per ET was statistically lower (15.2% vs. 26.2%, p = 0.004) belonging to DOR-Accu group. No statistical differences were found between the groups in regard to CLBR per ITT (20.4% vs. 27.5%, p = 0.081) despite of more mean surplus vitrified embryos per patient (1.18 embryos vs. 0.24 embryos, p < 0.001) for additional cryotransfers in DOR-Accu group. CLBR per OPU is statistically higher in DOR-fresh group (3.8% vs. 27.5%, p < 0.001). Table 1 Patient and cycle characteristics of the strategy for managing DOR compared between fresh M-II oocytes and accumulation of vitrified M-II oocytes Variable DOR-Accu DOR-fresh p Number of patient 211 229 Number of OPU 1130 229 OPU /patient Mean (SD) 5.36(2.71) 1.00(0.00) < 0.001* Maternal age at ART start Mean (SD) 39.29(4.23) 38.07(3.77) 0.001* Maternal age at ET Mean (SD) 40.23(4.30) 38.07(3.77) < 0.001* AMH Mean (SD) 0.54(0.35) 0.72(0.32) < 0.001* Reason for ART (%) DOR 211(100) 229(100) 1.00 Male factor 81(38.4) 98(42.8) 0.347 Tubal factor 39(18.5) 48(21.0) 0.515 Endometriosis 52(24.6) 52(22.7) 0.633 Unexplained or others 90(42.7) 93(40.6) 0.664 Number of total warmed or fresh M-II 2089 809 M-II oocytes /patient Mean (SD) 9.90 (4.77) 3.53 (1.57) < 0.001* Number of survival warmed or fresh M-II 1791 809 Number of fertilized egg 1317 582 Fertilization of survival and fresh egg % (SD) 75.18(20.98) 75.29(24.69) 0.958 ET Day (%) < 0.001* Day 2–3 174(82.5) 220(96.1) Day 4–5 37(17.5) 9(3.9) Number of fresh ET 211 229 Number of embryos transferred Mean (SD) 2.96(0.95) 2.14(0.87) < 0.001* Pregnancy /ET (%) 58(27.5) 71(31.0) 0.418 Implantation rate % (SD) 12.99(25.16) 17.47(29.52) 0.089 Miscarriage /pregnancy (%) 24(41.4) 10(14.1) < 0.001* Ectopic /pregnancy (%) 1(1.7) 0(1.4) 1.00 Still birth /ET (%) 1(1.7) 1(1.4) 1.00 Live birth /ET (%) 32(15.2) 60(26.2) 0.004* Number of surplus vitrified embryo embryo 248 55 Surplus vitrified embryo /patient Mean (SD) 1.18(1.80) 0.24(0.65) < 0.001* Cumulative live birth /ITT (%) 43(20.4) 63(27.5) 0.081 Cumulative live birth /OPU (%) 43(3.8) 63(27.5) < 0.001* * p < 0.05 Note: Data are mean ± standard deviation or n (%) and compared among groups using Student’s t- test, chi-square test, or Fisher’s test for P -value. Abbreviations: DOR-Accu = diminished ovarian reserve, accumulation of vitrified oocytes; DOR-fresh = diminished ovarian reserve, fresh oocytes; DOR = diminished ovarian reserve; OPU = ovum pick-up; ART = assisted reproduction technology; ET = embryo transfer; AMH = Anti-Müllerian hormone; M-II = metaphase II; ITT = intention to treat. Table 2 showed clinical outcomes were categorized in 4 groups in regard to patient’s age. Available M-II oocytes, embryos transferred per ET, and mean number of surplus vitrified embryo per patient were more in DOR-Accu group than in DOR-fresh group in all age groups. However, there is no difference in CPR between groups. Higher MR in DOR-Accu group aged 35–37 (33.3% vs. 7.7%, p = 0.048) and 38–40 (56.2% vs. 17.4%, p = 0.011) results in lower LBR per ET. MR of women aged over 40 in both groups was similarly high leading to low LBR. Similar fertilization, IR, and CLBR from DOR-Accu and DOR-fresh groups were observed in all age groups. CLBR per OPU was statistically higher in DOR-fresh group and was similarly poor in both groups aged over 40. Table 2 Clinical outcomes of the strategy for managing DOR according to patient’s age compared between fresh M-II oocytes and accumulation of vitrified M-II oocytes 40 Accu Fresh p Accu Fresh p Accu Fresh p Accu Fresh p Number of patients 28 36 38 55 57 74 88 64 Number of OPU 117 36 192 55 301 74 519 64 OPU /patient Mean (SD) 4.18 (2.13) 1 < 0.001* 5.05 (2.68) 1 < 0.001* 5.28 (2.32) 1 < 0.001* 5.91 (2.97) 1 < 0.001* Age at ART start (y), mean (SD) 31.89 (2.11) 31.86 (2.21) 0.954 36.03 (0.79) 36.09 (0.78) 0.696 39.11 (0.75) 38.84 (0.81) 0.055 43.17 (1.90) 42.36 (1.60) 0.01* M-II oocytes /patient Mean (SD) 8.50 (3.92) 3.64 (1.44) <0.001* 10.26 (5.33) 3.91 (1.34) < 0.001* 10.00 (4.32) 3.64 (1.67) < 0.001* 10.12 (5.03) 3.03 (1.62) < 0.001* Fertilization of fresh survival or M-II % (SD) 77.08 (22.51) 74.26 (24.00) 0.633 75.07 (16.25) 77.03 (22.16) 0.643 74.51 (24.18) 74.85 (23.64) 0.936 75.05 (20.37) 74.90 (28.54) 0.968 Number of fresh ET 28 36 38 55 57 74 88 64 Embryos transferred Mean (SD) 2.18 (0.82) 1.81 (0.58) 0.037* 2.58 (0.89) 2.33 (0.67) 0.123 3.02 (0.9) 2.27 (0.96) < 0.001* 3.33 (0.85) 2.00 (0.99) < 0.001 Pregnancy /ET (%) 10(35.7) 16(44.4) 0.481 18(47.4) 26(47.3) 0.993 16(28.1) 23(31.1) 0.709 14(15.9) 6(9.4) 0.239 Implantation rate % (SD) 25.00 (39.93) 30.56 (38.32) 0.574 24.78 (32.68) 26.67 (32.01) 0.782 12.28 (21.08) 15.43 (27.12) 0.471 4.55 (10.64) 4.56 (16.19) 0.996 Miscarriage /ET (%) 1(10.0) 1(6.2) 1.000 6(33.3) 2(7.7) 0.048* 9(56.2) 4(17.4) 0.011* 8(57.1) 3(50.0) 1.000 Live birth /ET (%) 8(28.6) 15(41.7) 0.279 11(28.9) 23(41.8) 0.205 7(12.3) 19(25.7) 0.057 6(6.8) 3(4.7) 0.735 Number of surplus vitrified embryo 37 16 85 19 65 17 61 3 Surplus vitrified embryo /patient Mean (SD) 1.32 (1.83) 0.44 (0.73) 0.011* 2.24 (2.60) 0.35 (0.73) < 0.001* 1.14 (1.44) 0.23 (0.75) < 0.001* 0.69 (1.36) 0.05 (0.28) 0.001* Cumulative live birth /ITT (%) 13(46.4) 16(44.4) 0.874 15(39.5) 24(43.6) 0.689 8(14.0) 20(27.0) 0.072 7(8.0) 3(4.7) 0.520 Cumulative live birth /OPU (%) 13(11.1) 16(44.4) < 0.001* 15(7.8) 24(43.6) < 0.001* 8(2.7) 20(27.0) < 0.001* 7(1.3) 3(4.7) 0.086 * p < 0.05 Note: Data are mean ± standard deviation or n (%) and compared among groups using Student’s t- test, chi-square test, or Fisher’s test for P -value. Abbreviations: Accu = accumulation of vitrified oocytes; fresh = Fresh oocytes; DOR = diminished ovarian reserve; OPU = ovum pick-up; ART = assisted reproduction technology; M-II = metaphase II; ET = embryo transfer; ITT = intention to treat. Table 3 showed clinical outcome of patient accumulated vitrified M-II oocytes reach the goal of total number ≥ 10 and ≥ 15. More mean number of available M-II oocytes to create more embryos for ET in DOR-Accu group contribute to increasing CPR (48.4% vs. 31.0%, p = 0.054), but it fail to improve LBR per ET (29.0% vs. 26.2%, p = 0.738) and CLBR per ITT (29.0% vs. 27.5%, p = 0.859). Therefore, higher MR (40.0% vs. 14.1%, p = 0.03) in DOR-Accu group was still notable. Table 3 Clinical outcomes of the strategy for managing DOR compared between fresh oocytes and accumulated vitrified oocytes reach ≥ 10 or ≥ 15 M-II oocytes DOR-fresh (A) DOR-Accu p ≥ 10 M-II (B) ≥ 15 M-II (C) A vs B A vs C Number of patient 229 100 31 Number of OPU 229 654 256 OPU /patient Mean (SD) 1.00(0.00) 6.54(3.04) 8.26(3.60) < 0.001* < 0.001* Maternal age at ART start Mean (SD) 38.07(3.77) 39.75(3.78) 39.26(3.61) < 0.001* 0.098 AMH Mean (SD) 0.72(0.32) 0.57(0.34) 0.67(0.32) < 0.001* 0.376 M-II oocytes /patient Mean (SD) 3.53(1.57) 13.57(4.14) 18.61(3.79) < 0.001* < 0.001* Fertilization of fresh and survival egg % (SD) 75.29(24.69) 71.88(18.37) 73.31(12.91) 0.215 0.662 Number of transfer cycle 229 100 31 Number of embryos transferred Mean (SD) 2.14(0.87) 3.26(0.82) 3.26(0.86) < 0.001* < 0.001* Pregnancy /ET (%) 71(31.0) 36(36.0) 15(48.4) 0.374 0.054 Implantation rate % (SD) 17.47(29.52) 18.08(28.58) 26.34(34.57) 0.861 0.125 Miscarriage /pregnancy (%) 10(14.1) 15(41.7) 6(40.0) 0.001* 0.030* Still birth /pregnancy (%) 1(1.7) 0(0.0) 0(0.0) 1.00 1.00 Live birth /ET (%) 60(26.2) 21(21.0) 9(29.0) 0.314 0.738 Number of surplus vitrified embryo 55 179 85 Surplus vitrified embryo /patient Mean (SD) 0.24(0.65) 1.79(2.18) 2.74(2.58) < 0.001* < 0.001* Cumulative live birth /ITT (%) 63(27.5) 26(26.0) 9(29.0) 0.777 0.859 Cumulative live birth /OPU (%) 63(27.5) 26(4.0) 9(3.5) < 0.001* < 0.001* * p < 0.05 Note: Data are mean ± standard deviation or n (%) and compared among groups using Student’s t- test, chi-square test, or Fisher’s test for P -value. Abbreviations: DOR-fresh = diminished ovarian reserve, fresh oocytes; DOR-Accu = diminished ovarian reserve, accumulation of vitrified oocytes; DOR = diminished ovarian reserve; M-II = metaphase II; OPU = ovum pick-up; ART = assisted reproduction technology; AMH = Anti-Müllerian hormone; ET = embryo transfer; ITT = intention treat. Table 4 evaluated whether age, AMH, managing DOR strategy, and number of embryos transferred affect clinical outcomes. Although maternal age of ART start and ET were older and AMH was lower in DOR-Accu group compared with DOR-fresh group (Table 1 ), it did not affect clinical outcomes. However, a vitrified oocytes accumulation strategy had negative effects on MR per pregnancy (OR: 4.00, 95% CI = 1.10–14.58) and LBR per ET (OR: 0.42, 95% CI = 0.20–0.89). LBR per ET improved as more embryos transfer: 2 embryos (OR: 3.40, 95% CI = 1.41–8.18), 3 embryos (OR: 3.19, 95% CI = 1.25–8.10), and 4 embryos (OR: 5.94, 95% CI = 1.99–17.71). Table 4 The effect of the relevant significant variables on clinical outcomes CPR Adj-OR (95%CI) p MR Adj-OR (95%CI) p LBR Adj-OR (95%CI) p Maternal age at ET ✝ 0.71 (0.46–1.10) 0.125 0.94 (0.42–2.12) 0.884 0.84 (0.50–1.42) 0.523 Maternal age at ART start ✝ 1.18 (0.77–1.82) 0.448 1.44 (0.65–3.15) 0.368 0.97 (0.58–1.64) 0.914 AMH ✝ 0.81 (0.41–1.63) 0.561 0.78 (0.17–3.47) 0.739 0.98 (0.44–2.17) 0.955 Strategy # 0.478 0.036* 0.022* Fresh IVF 1 1 1 Accumulated vitrified M-II 0.80 (0.44–1.48) 0.478 4.00 (1.10-14.58) 0.036* 0.42 (0.20–0.89) 0.022* Number of Embryos transferred # < 0.001* 0.327 0.013* 1 1 1 1 2 4.23 (1.80–9.97) 0.001* 0.00 (0.00-Inf) 0.99 3.40 (1.41–8.18) 0.006* 3 6.48 (2.67–15.72) < 0.001* 0.00 (0.00-Inf) 0.99 3.19 (1.25–8.10) 0.015* 4 9.07 (3.30-24.91) < 0.001* 0.00 (0.00-Inf) 0.99 5.94 (1.99–17.71) 0.001* * p < 0.05 ✝ Continuous variables # Categorical variables Linear regression was used to analyze continuous variables and logistic regression was used to evaluate categorical variables. Each variables was adjusted for the strategy for managing DOR, AMH, the number of embryos transferred, ET day, maternal age at ET and ART start. Abbreviations: CPR = clinical pregnancy rate; MR = miscarriage rate; LBR = live birth rate; ET = embryo transfer; ART = assisted reproduction technology; AMH = Anti-Müllerian hormone; IVF = in vitro fertilization; M-II = metaphase II; ET = embryo transfer. Discussion This study showed that DOR women used the vitrified oocytes accumulation strategy to obtain more embryos for transfer fails to improve CPR, and statistically higher MR results in lower LBR per ET. More surplus vitrified embryo did not also improve CLBR. Vitrification-thawing oocytes presented 85.7% survival rate. Based on survival rates of thawing oocytes described in previous studies [ 4 , 6 – 14 , 16 , 18 , 20 , 21 , 34 ], we concluded that vitrification-thawing program has been standardized. Vitrified oocytes is a mature technology for reproduction preservation and has similar outcomes to fresh oocytes in donor women [ 6 – 16 ]. But intracellular ice crystals formation, solution effects, and osmotic shock which cause oocytes damage still exit during cryopreservation. DNA fragmentation, chromosome disorganization, aberrant gene expression, and damage to mitochondria, endoplasmic reticulum, and lysosomes have been also found in oocytes after cryopreservation [ 25 – 27 , 35 – 40 ]. Meiotic spindle is determinant of oocyte viability, poor spindle architecture impact chromosome stability, fertilization, and possible embryonic development and results in high aneuploidy levels which cause embryo degeneration and spontaneous abortion [ 41 – 47 ]. Disappearance and reappearance of the meiotic spindle occur during cooling-thawing procedure, and temperature fluctuations as small as 0.3°C for short times can cause irreversible spindle damage [ 47 – 50 ]. Aberrant spindles are frequently found in oocytes obtained from women of advanced reproductive age [ 44 , 45 ], and it may cause oocytes from older women who are more vulnerable to cryopreservation damage. Our results showed that women aged over 35 in DOR-Accu group has relative high abortion rate compared with DOR-fresh group. It may approve this speculation. Spindle architecture in oocytes from women younger than 35 is healthy and suffers less damage from cooling and thawing. Therefore, MR was comparable to fresh oocytes. We set goal of accumulating total number 10–15 M-II oocytes in DOR-Accu group which was expected to get higher CPR than in fresh oocyte cycle. However, only 100 patients (47.4%) accumulated vitrified oocytes reached total number ≥ 10 and 31 patients (14.7%) reached total number ≥ 15. This can be attributed to DOR that yielded low oocytes count despite double stimulation in same ovarian cycle maximize oocytes output [ 29 , 30 ]. Patients need to receive repeat ovarian stimulation and retrieval 8.26 times to reach total number ≥ 15 of accumulation. Although vitrified oocytes accumulation strategy may palliate DOR women the psychological distress that caused by repeated transfer failures [ 4 ], they still distress from stimulation cancellation, repeat invasive procedure, and failure retrieving which discourage them from accumulating enough vitrified M-II oocytes. Cost and risk of repeat ovarian stimulation and retrieval could be higher in DOR-Accu group, even in mild COS with flexible gonadotropins use. Even DOR women who accumulate vitrified M-II oocytes reach total number ≥ 15 and create more embryos to improve CPR, higher MR (40%) counterbalance it, and result in similar LBR and CLBR per ITT compared with DOR-fresh group. Although, vitrified M-II oocytes need average 6–9 times of OPU to get similar LBR and CLBR to 1 IVF cycle using fresh oocytes, it is a poorly cost-effective strategy for managing DOR. Previous studies showed vitrified oocytes accumulation strategy inseminated vitrified oocytes that pooled together with fresh oocytes got similar outcomes compared with IVF cycle using fresh oocytes [ 4 , 5 ]. More poor outcomes per ET or per OPU are expected if only accumulated vitrified oocytes were used. It is noteworthy that CLBR was poor in both groups as women aged over 40 (8.0% vs. 4.7%, p = 0.52). It is not surprising because previous research reported CLBR from patients who underwent elective fertility preservation worsened dramatically after age of 40 years (3.7%) [ 51 ], and our data showed similar result. In our unpublished data, 14 young women aged ≤ 37 year who accumulated at least 10 vitrified M-II oocytes could achieve statistically higher CLBR (77.8% vs. 45.8%, p = 0.015) than DOR-fresh group. CLBR were poor in both group after age of 37 years regardless of number of accumulating vitrified M-II oocytes. Moreover, there were 28 patients who underwent 229 ovum retrievals and harvested 170 oocytes, and these extremely DOR women who obtained less than mean one M-II oocyte per OPU all got no live birth finally. However, we need to extend sample size and performed randomized controlled trial to approve observation results and make conclusion. Our study has some limitation. It is a retrospective review of patient who had obtained oocytes from retrieval in both groups and we did not include patients who had no embryos transferred for any cause. We did not calculate cycle cancellation rate and patient dropout rate and just focused on transfer outcomes. It pointed out that average age at ART start and ET was older, and average AMH serum levels were lower in DOR-Accu group. However, these differences between groups were too minimal to confound clinical outcomes, and it was also approved in Table 4 . Moreover, statistically higher MR (40.0% vs. 14.1%, p = 0.03), similar LBR (29.0% vs. 26.2%, p = 0.738), and CLBR (29.0% vs. 27.5%, p = 0.738) exist in subgroup of patient accumulated vitrified oocytes reach ≥ 15 M-II oocytes despite similar age at ART start and AMH serum levels in two groups. Conclusion Our result demonstrated that accumulation of oocytes by vitrification for DOR women fail to improve LBR even accumulation reach total number ≥ 15 vitrified M-II oocytes. Moreover, higher MR (41.4%) in DOR-Accu group resulted in lower LBR (15.2% vs. 26.2%, p = 0.004). It is difficult to accumulate vitrified M-II oocytes to reach total number ≥ 15 because only 14.7% achieved the goal. Even if patients reach this goal of accumulating vitrified M-II oocytes, it took average of 8.26 times of OPU to get similar LBR per ET and CLBR to that from 1 IVF cycle using fresh oocytes. Accumulating vitrified M-II oocytes is less efficient and has lower efficacy than IVF cycles using fresh oocytes for managing DOR. Abbreviations Live birth rate (LBR), diminished ovarian reserve (DOR), Anti-Müllerian hormone (AMH), antral follicle count (AFC), diminished ovarian reserve accumulation of vitrified oocytes (DOR-Accu), embryo transfer (ET), controlled ovarian stimulation (COS), diminished ovarian reserve fresh oocytes (DOR-fresh), cumulative LBR (CLBR), intention to treat (ITT), clinical pregnancy rate (CPR), miscarriage rate (MR), metaphase II (M-II), Poor ovarian responders (POR), in vitro fertilization (IVF), assisted reproduction technology (ART), gonadotropin-releasing hormone (GnRH), vitrification solution (VS), warming solution (TS), washing solution (WS), intracytoplasmic sperm injection (ICSI), estradiol (E2), implantation rate (IR), odds ratios (OR), confidence intervals (CIs) Declarations Ethics approval and consent to participate The study protocol was approved by Institutional Review Board of Mackay Memorial Hospital (21MMHIS219e). There is no participants consent for this retrospective study and Institutional Review Board decide this is ethically acceptable. Consent for publication Not applicable. Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests Funding Statement This research received no external financial support from any commercial company. Authors’ contributions K-S L and R K-K L were involved in the conception and design of the study; K-S L, M-H L, Y-M H and R K-K L were involved in collected patients in MacKay Memorial Hospital; K-S L, J-H Y contributed to data analysis and interpretation; K-S L, M-H L and R K-K L were involved in routine meeting and advising the study design; R K-K L as co-corresponding authors, had the major roles in designing the manuscript, interpreting the analyzed data, advising, drafting, and revising the draft. All authors were involved in the writing of the manuscript and provided final approval. Acknowledgements The authors thank the medical staff of MacKay Memorial Hospital for involvement and Rufina D for English editing and proofreading in the study. References Devine K, Mumford SL, Wu M, DeCherney AH, Hill MJ, Propst A. 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Oocyte maturation, embryo development and gene expression following two different methods of bovine cumulus-oocyte complexes vitrification. Vet Res Commun 2017; 41:49–56. Poseidon Group (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number), Alviggi C, Andersen CY, et al . A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept. Fertil Steril 2016; 105: 1452–1453. Alberto Vaiarelli, Danilo Cimadomo, Alessandro Conforti, Mauro Schimberni, Maddalena Giuliani, Pietro D'Alessandro, Silvia Colamaria, Carlo Alviggi, Laura Rienzi, Filippo Maria Ubaldi. Luteal phase after conventional stimulation in the same ovarian cycle might improve the management of poor responder patients fulfilling the Bologna criteria: a case series. Fertil Steril. 2020;113(1):121–130 Yanping Kuang, Qiuju Chen, Qingqing Hong, Qifeng Lyu, Ai Ai, Yonglun Fu, Zeev Shoham. 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Limited recovery of meiotic spindles in living human oocytes after cooling-rewarming observed using polarized light microscopy. Hum Reprod. 2001;16(11):2374–8. Ana Cobo, Juan A García-Velasco, Aila Coello, Javier Domingo, Antonio Pellicer, José Remohí. Oocyte vitrification as an efficient option for elective fertility preservation. Fertil Steril 2016;105(3):755–764.e8. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1482330","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":93454296,"identity":"ad661fe1-aab2-44a8-920d-700aa9cac943","order_by":0,"name":"Kuan-Sheng Lee","email":"","orcid":"","institution":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics \u0026 Gynecology, MacKay Memorial Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kuan-Sheng","middleName":"","lastName":"Lee","suffix":""},{"id":93454297,"identity":"d4523e91-e635-4fe7-9eef-f8db38d968b2","order_by":1,"name":"Ming-Huei Lin","email":"","orcid":"","institution":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics \u0026 Gynecology, MacKay Memorial Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ming-Huei","middleName":"","lastName":"Lin","suffix":""},{"id":93454298,"identity":"fc8a18c2-2910-42fc-81ac-4c252b3604ce","order_by":2,"name":"Yuh-Ming Hwu","email":"","orcid":"","institution":"Taipei Fertility Center (TFC)","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yuh-Ming","middleName":"","lastName":"Hwu","suffix":""},{"id":93454299,"identity":"e61916e1-af79-4ec2-8e48-08aa3748914d","order_by":3,"name":"Jia-Hwa Yang","email":"","orcid":"","institution":"Taiwan Public Health Association","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jia-Hwa","middleName":"","lastName":"Yang","suffix":""},{"id":93454300,"identity":"10a72316-2388-4bee-83b3-964caffdfba9","order_by":4,"name":"Robert Kuo-Kuang Lee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIiWNgGAWjYDACZubDj/8Y2NT3MzM2PgDyefgIamFvSzPgqUhjnNne3GwA0sJGUAvPGQMJnjOHGDf0HG+TAAkQ1MI/I8fAQLLtALOBRGJb5dccOxk2BuaHj27g0SJxI63ggWHbHTZzoJbbstuSgQ5jMzbOwWfNjeQNBoltz3gsZwC1SG5jBmrhYZPGp0X+RoKBxMG2wxIGNxLbiiW31RPWYnDmiIFkw5nDBgZnDrYxftx2mLAWw+NtacYMFWkJku2NzdKM247zsDET8IvcYWBUMhjYJPAzsz/8+HNbtT0/e/PDx3i9jwyYecAkscpBgPEHKapHwSgYBaNgxAAAwQ9NhGSk7dkAAAAASUVORK5CYII=","orcid":"","institution":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics \u0026 Gynecology, MacKay Memorial Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Robert","middleName":"Kuo-Kuang","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2022-03-23 15:29:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1482330/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1482330/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":21820123,"identity":"f941fd90-ff57-43f8-b725-ce4db558b747","added_by":"auto","created_at":"2022-05-24 12:14:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":364348,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1482330/v1/2aa68839-00ea-4ffe-b356-636e00c92ae9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Outcomes of Vitrified Oocytes Accumulation for Managing Diminished Ovarian Reserve: A retrospective cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePoor ovarian responders (POR) or DOR are encountered during infertility treatment, and poor prognosis during improves in vitro fertilization (IVF) treatment is ascribed with it [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Vitrified M-II oocytes accumulation strategy for later simultaneous insemination has been used for managing POR since two studies reported that it improved IVF outcome [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In patients with POR, current data came from vitrified oocytes accumulation were pooled together with fresh oocytes. It caused a difficulty in determining contribution of CPR and LBR from pooling together vitrified oocytes or fresh oocytes. We determined whether vitrified oocytes accumulation strategy from DOR women improves LBR in assisted reproduction technology (ART).\u003c/p\u003e \u003cp\u003eNumerous randomized controlled trials and prospective and retrospective studies have shown that cryopreserved oocytes provide reproductive outcomes comparable to fresh oocytes use [\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, large cohort analysis has indicated overall lower reproductive outcomes using vitrified donor oocytes rather than using fresh donor oocytes [\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The alterations have been found in gene expression and reduced mitochondrial DNA content in vitrified and thawed oocytes [\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Despite of extensive literature examining cryopreserved oocyte quality clinical characteristics, there is still lacking data regarding whether ART outcomes of using vitrified and thawed oocytes from DOR women is comparable with using fresh oocytes from DOR women.\u003c/p\u003e \u003cp\u003eTherefore, the study objective was to evaluate whether vitrified oocytes accumulation for later simultaneous insemination improve LBR to manage DOR.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA medical record review was performed for DOR woman who underwent COS and ET using vitrified oocytes accumulation for later simultaneous insemination or using fresh oocytes at Infertility Division of Mackay Memorial Hospital in Taipei City, Taiwan from January 1, 2014 to December 31, 2019. The patients were followed during treatment at our center for at least 1 year until either treatment discontinuation or 1 live infant delivery. The study protocol was approved by Institutional Review Board of Mackay Memorial Hospital (21MMHIS219e). \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDOR was made in accordance with the Poseidon (\u003cstrong\u003eP\u003c/strong\u003eatient-\u003cstrong\u003eO\u003c/strong\u003eriented \u003cstrong\u003eS\u003c/strong\u003etrategies \u003cstrong\u003eE\u003c/strong\u003encompassing \u003cstrong\u003eI\u003c/strong\u003endividualize\u003cstrong\u003eD\u003c/strong\u003e \u003cstrong\u003eO\u003c/strong\u003eocyte \u003cstrong\u003eN\u003c/strong\u003eumber) classification groups 3 and 4 [28], defined as presence of low serum AMH hormone level (\u0026lt;1.2 ng/ml) or low AFC (\u0026lt;5) at time of ovarian stimulation initiation. All patients who met the criteria of Poseidon Groups 3 and 4 and had at least 1 embryo created intended to transfer during current cycle were included.\u003c/p\u003e\n\u003cp\u003eExclusion criteria were coexisting endocrine disorders (diabetes mellitus, untreated hyperprolactinemia, untreated thyroid dysfunction, congenital adrenal hyperplasia, and Cushing\u0026rsquo;s syndrome), untreated hydrosalpinx, and uterine anomaly confirmed either by hysterosalpingography or hysteroscopy. After applying the exclusion criteria, a total of 440 DOR women who underwent fresh ET were included for final analysis. The study group included 211 patients with vitrified M-II oocytes accumulation for later simultaneous insemination. This group was named \u0026ldquo;diminished ovarian reserve, accumulation of vitrified oocytes\u0026rdquo; (DOR-Accu). In this group, we used double stimulation in same ovarian cycle to maximize the oocytes number retrieved in a short time frame [29, 30]. After oocyte retrieval, all mature oocytes were vitrified and stored. Luteal phase ovarian stimulation following oocyte retrieval was performed based on number of remainder AFC. The decision about whether to stop oocytes accumulation was based on two factors as follows: (1) the vitrified M-II oocytes total number reaches 10\u0026ndash;15 which was expected to maximize the LBR [31-33] and (2) the patient\u0026rsquo;s own decision.\u003c/p\u003e\n\u003cp\u003eThe control group included 229 DOR patients who underwent gonadotropin-releasing hormone (GnRH) agonist-flare protocol or GnRH antagonist protocol, whose fresh mature oocytes were inseminated and subsequent ET was named \u0026ldquo;diminished ovarian reserve, fresh oocytes\u0026rdquo; (DOR-fresh). Surplus embryos in both groups had been vitrified and transferred in their subsequent cycle until surplus embryos exhaust or patient gets at least 1 live infant delivery. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOvarian Stimulation Protocols\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePeople in the DOR-fresh group using GnRH antagonist or GnRH agonist-flare protocol. Patients using GnRH agonist-flare or GnRH antagonist protocol started 300\u0026ndash;450 IU recombinant FSH (Gonal-F; Merck Serono) or follitropin \u0026beta; (Puregon\u003csup\u003e\u0026reg;\u003c/sup\u003e; Organon) either alone or in combination with human menopausal gonadotropin (Menopur; Ferring) on day 2\u0026ndash;3 of menstrual cycle. Patients using mild stimulation received oral compound such as letrozole (Femara; Genepharm S.A) 5 mg/day prior to gonadotropin stimulation on day 2\u0026ndash;6 of menstrual cycle and followed by stimulation with 150 IU/day subcutaneous gonadotropin (Gonal-F or human menopausal gonadotropin or Puregon) on day 7 of menstrual cycle. In the GnRH agonist protocol, pituitary flare up with 0.5 mg subcutaneous leuprolide acetate (Takeda Pharma GmbH, Stolberg, Germany) beginning on day 2 of menstrual cycle until trigger day. In GnRH antagonist protocol, 0.25 mg subcutaneous cetrorelix (Cetrotide; Merck Serono) was administered daily when follicles reached \u0026ge; 14 mm in diameter until trigger day. The gonadotropin dosage was adjusted every 2\u0026ndash;3 days in accordance with follicle growth.\u003c/p\u003e\n\u003cp\u003ePeople in the DOR-Accu group using double stimulations in same menstrual cycle with gonadotropins and clomiphene or letrozole combination. In follicle phase stimulation, clomiphene citrate 150 mg/day or letrozole 7.5 mg/day were given on day 2\u0026ndash;3 of menstrual cycle onward. Gonadotropin 150\u0026ndash;450 IU/day was added later when 3 three follicles reached \u0026gt;10 mm in diameter and 0.25-mg subcutaneous cetrorelix (Cetrotide; Merck Serono) was administered in presence of 14-mm follicle until trigger day. Transvaginal ultrasound was performed after oocyte retrieval, and clomiphene citrate 150 mg/day or letrozole (7.5 mg/day) was given in presence of 1 AFC. Gonadotropin 150\u0026ndash;450 IU/day was added when 3 three follicles reached 10 mm until trigger day. GnRH antagonist was administered as follicular phase. When leading follicle reached 18 mm in diameter, final oocyte maturation was triggered by combination of 250-\u0026mu;g recombinant hCG (Ovidrel; Merck Serono) and 0.2-mg triptorelin (Decapeptyl; Ferring). Oocyte retrievals were performed under transvaginal ultrasound guidance, 35 to 36 h post triggering.\u003c/p\u003e\n\u003cp\u003eThe oocytes from DOR-Accu group were vitrificated by 3-step gradient cryoprotectant loading process using Cryotec Vitrification Method\u0026reg; (REPROLIFE Inc. 2-5-3-9F Shinjuku, Tokyo, Japan). The oocytes were equilibrated for 12\u0026ndash;15 mins in 0.3-ml equilibration solution. Then oocytes were washed in a 0.3-ml vitrification solution (VS) for 30\u0026ndash;40 secs and replaced with new 0.3-ml VS for another 10\u0026ndash;20 secs. In next step, oocytes were loaded on Cryotec seat with minimum (0.01\u0026ndash;0.1\u0026mu;l) VS volume and immediately submerge Cryotec into liquid nitrogen directly and then cover with cap. All procedure was performed at room temperature (25\u0026deg;C\u0026ndash;27\u0026deg;C) with media being prepared at least 1 h in advance.\u003c/p\u003e\n\u003cp\u003eFirstly, warming procedure (REPROLIFE Inc. 2-5-3-9F Shinjuku, Tokyo, Japan) started with Cryotec removal from liquid nitrogen and its immersion in 1-ml warming solution (TS) for 1 min. Secondly, oocytes were transferred into 0.3-ml dilution solution for 3 minutes. Thirdly, oocytes were equilibrated in 0.3-ml washing solution (WS) for another 5 minutes and replaced with a new 0.3-ml WS for another 1 min. Finally, oocytes were incubated in culture media for 2 h at 37\u0026deg;C, 6.0% CO\u003csub\u003e2\u003c/sub\u003e, and 5% O\u003csub\u003e2\u003c/sub\u003e before intracytoplasmic sperm injection (ICSI). TS was placed in incubator at 37\u0026deg;C at least 3 h before use, and other two were prepared 1 h at room temperature (25\u0026deg;C\u0026ndash;27\u0026deg;C) in advance. All warming procedure was also performed at room temperature. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInsemination and Embryo Transfer\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWarmed oocytes were cultured for 3 h prior to ICSI. Fresh oocytes were denudated immediately following oocyte retrieval. In vitro insemination procedures were performed 38 to 39 h post triggering for fresh oocytes, with exceptions in male factor, which ICSI were performed instead. Assisted hatching was performed to improve embryo capacity to implant. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEndometrial Preparation,\u003c/strong\u003e\u003cstrong\u003e Luteal Phase Support, and Pregnancy Con\u003c/strong\u003e\u003cstrong\u003efi\u003c/strong\u003e\u003cstrong\u003ermation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn DOR-fresh group, patients received 50-mg progesterone on oocyte retrieval day. Then, plus 125-\u0026mu;g intramuscular injection recombinant hCG (Ovidrel; Merck Serono) every 3 days plus daily vaginal supplementation of 90-mg vaginal progesterone gel (Crinone 8%; Merck Serono) or oral 10-mg dydrogesterone (Duphaston\u003csup\u003e\u0026reg;\u003c/sup\u003e; Abbott Biologicals) every 8 h plus 2-mg oral estradiol (E2) valerate (Progynova; \u003cem\u003eSynmosa Biopharma\u003c/em\u003e Corporation) every 8 h plus vaginal supplementation of 90-mg vaginal progesterone gel (Crinone 8%; Merck Serono) every 12 h started on day 1 after oocyte retrieval as following luteal phase support.\u003c/p\u003e\n\u003cp\u003e In DOR-Accu group, endometrial preparation was started with oral estradiol (E2) valerate (Progynova; \u003cem\u003eSynmosa Biopharma\u003c/em\u003e Corporation) 8mg daily on day 1\u0026ndash;3 of menstrual cycle. After 7 days of oral estrogen supplementation, we started to perform ultrasound to measure endometrial thickness. If endometrium was thinner than 7 mm at day 8, we increased estrogen dose to 12 mg daily followed by a reevaluation with ultrasound on day 13 of estrogen supplementation. If endometrium had reached at least 7 mm, all vitrified oocytes were warmed and inseminated by ICSI. We continued oral estrogen 8 mg daily and started 90-mg vaginal progesterone gel (Crinone 8%; Merck Serono) every 12 h plus 10-mg oral dydrogesterone (Duphaston\u003csup\u003e\u0026reg;\u003c/sup\u003e; Abbott Biologicals) every 8 h since the inseminated oocytes day (day 0). If endometrium had reached 7 mm or more, oocytes thawing, endometrial preparation, and luteal phase support started on day 1 after thawing oocytes were done as mention before.\u003c/p\u003e\n\u003cp\u003eAfter oocytes retrieval or oocytes thawing, serum \u0026beta;-hCG was measured 14 days later, or urine hCG was checked 16 days later. Serum \u0026beta;-hCG above 5 mIU/mL or urine hCG above 25 mIU/mL was considered to be a positive pregnancy. Luteal support was continued until 10th week of gestation. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary and Secondary Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study\u0026rsquo;s primary outcomes were LBR per ET and CLBR per ITT. Secondry outcomes included oocyte survival rate, fertilization rate, mean number of embryos transferred, CPR per ET, implantation rate (IR), MR per pregnancy, mean number of surplus vitrified embryo, and CLBR per OPU. A subgroup analysis was conducted on cases reach total number \u0026ge; 10 and \u0026ge; 15 M-II oocytes. To control repeat ET confounding factor, we only include last cycle with ET for final analysis if patients underwent repeat IVF cycle or repeat vitrified oocytes accumulation for later simultaneous insemination. LBR was defined as number of delivery resulted in a live born neonate who reached 20-weekgestational age per ET. CLBR calculated live birth until either cryotransfers of all embryos or 1 live infant delivery fertilization was assessed 16\u0026ndash;18 h after insemination by visualization of 2 pronuclei and 2 polar bodies. CPR was defined as presence of at least 1 gestational sac between 5\u003csup\u003eth\u003c/sup\u003e and 6\u003csup\u003eth\u003c/sup\u003e weeks of gestation in ultrasound per ET. IR was calculated by dividing total number of gestational sac detected by total number of transferred embryos. MR was defined as spontaneous loss of all intrauterine pregnancy prior to completed 20-week gestational age. For OPU number, we only count retrievals, at least 1 M-II oocytes was available for later insemination. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analysis was performed with R software, version 3.3.1 (R Project for Statistical Computing, Vienna, Austria). Differences in demographics among two groups were assessed with Student\u0026rsquo;s \u003cem\u003et-\u003c/em\u003etest, chi-square, or Fisher\u0026rsquo;s test, and results for continuous variables were presented as mean standard deviation; whereas, categorical variables were expressed as percentages. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were calculated by logistic regression analysis with relevant significant variables adjustment to assess effect of age, strategy, AMH, number of embryos transferred, and ET day on clinical outcomes. The 95% CIs for differences between proportions were calculated for LBR. Statistical significance was defined at 95% level (P \u0026lt; 0.05).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e showed mean age at ART start were older in DOR-Accu group (39.29y vs. 38.07y, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and mean AMH were lower in DOR-Accu group (0.54 ng/ml vs. 0.72 ng/ml, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) than the DOR-fresh group. There is no difference in reason for ART between groups. In DOR-fresh group, total of 229 women obtained 809 mature oocytes, resulting in mean 3.53 M-II oocytes for insemination. The DOR-Accu group consisted of 211 patients who received 1,130 stimulation and oocyte retrieval cycles, resulting in mean 5.36 cycles per woman. A total number of 2,089 M-II oocytes were retrieved and vitrified. These oocytes were warmed, and 1,791 survival M-II oocytes (survival rate: 85.7%) were submitted to ICSI. Fertilization rates, CPR, and IR in the DOR-Accu group were similar to DOR-fresh group. Mean number of embryos transferred per cycle was more in DOR-Accu group (2.96 vs. 2.14, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). MR was statistically higher (41.4% vs. 14.1%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and LBR per ET was statistically lower (15.2% vs. 26.2%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004) belonging to DOR-Accu group. No statistical differences were found between the groups in regard to CLBR per ITT (20.4% vs. 27.5%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.081) despite of more mean surplus vitrified embryos per patient (1.18 embryos vs. 0.24 embryos, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for additional cryotransfers in DOR-Accu group. CLBR per OPU is statistically higher in DOR-fresh group (3.8% vs. 27.5%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n\u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003ePatient and cycle characteristics of the strategy for managing DOR compared between fresh M-II oocytes and accumulation of vitrified M-II oocytes\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003eDOR-Accu\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003eDOR-fresh\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eNumber of patient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e229\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eNumber of OPU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e1130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e229\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eOPU /patient Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e5.36(2.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e1.00(0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 1.0145%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eMaternal age at ART start Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e39.29(4.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e38.07(3.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eMaternal age at ET Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e40.23(4.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e38.07(3.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eAMH Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e0.54(0.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e0.72(0.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eReason for ART (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eDOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e211(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e229(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eMale factor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e81(38.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e98(42.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.347\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eTubal factor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e39(18.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e48(21.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.515\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eEndometriosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e52(24.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e52(22.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.633\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eUnexplained or others\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e90(42.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e93(40.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.664\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eNumber of total warmed or fresh M-II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e2089\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e809\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eM-II oocytes /patient Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e9.90 (4.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e3.53 (1.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eNumber of survival warmed or fresh M-II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e1791\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e809\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eNumber of fertilized egg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e1317\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e582\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eFertilization of survival and fresh egg % (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e75.18(20.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e75.29(24.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.958\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eET Day (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eDay 2\u0026ndash;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e174(82.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e220(96.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eDay 4\u0026ndash;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e37(17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e9(3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eNumber of fresh ET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e229\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eNumber of embryos transferred Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e2.96(0.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e2.14(0.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003ePregnancy /ET (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e58(27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e71(31.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.418\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eImplantation rate % (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e12.99(25.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e17.47(29.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eMiscarriage /pregnancy (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e24(41.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e10(14.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eEctopic /pregnancy (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e1(1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e0(1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eStill birth /ET (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e1(1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e1(1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eLive birth /ET (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e32(15.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e60(26.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.004*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eNumber of surplus vitrified embryo embryo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e248\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eSurplus vitrified embryo /patient Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e1.18(1.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e0.24(0.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eCumulative live birth /ITT (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e43(20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e63(27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 28.7294%;\"\u003e\n \u003cp\u003eCumulative live birth /OPU (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e43(3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\n \u003cp\u003e63(27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 1.0145%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 42.0966%;\"\u003e\n \u003cp\u003e* \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 13.3672%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 8.1799%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 65.0402%;\"\u003eNote: Data are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or n (%) and compared among groups using Student\u0026rsquo;s \u003cem\u003et-\u003c/em\u003etest, chi-square test, or Fisher\u0026rsquo;s test for \u003cem\u003eP\u003c/em\u003e-value. Abbreviations: DOR-Accu\u0026thinsp;=\u0026thinsp;diminished ovarian reserve, accumulation of vitrified oocytes; DOR-fresh\u0026thinsp;=\u0026thinsp;diminished ovarian reserve, fresh oocytes; DOR\u0026thinsp;=\u0026thinsp;diminished ovarian reserve; OPU\u0026thinsp;=\u0026thinsp;ovum pick-up; ART\u0026thinsp;=\u0026thinsp;assisted reproduction technology; ET\u0026thinsp;=\u0026thinsp;embryo transfer; AMH\u0026thinsp;=\u0026thinsp;Anti-M\u0026uuml;llerian hormone; M-II\u0026thinsp;=\u0026thinsp;metaphase II; ITT\u0026thinsp;=\u0026thinsp;intention to treat.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e showed clinical outcomes were categorized in 4 groups in regard to patient\u0026rsquo;s age. Available M-II oocytes, embryos transferred per ET, and mean number of surplus vitrified embryo per patient were more in DOR-Accu group than in DOR-fresh group in all age groups. However, there is no difference in CPR between groups. Higher MR in DOR-Accu group aged 35\u0026ndash;37 (33.3% vs. 7.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048) and 38\u0026ndash;40 (56.2% vs. 17.4%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011) results in lower LBR per ET. MR of women aged over 40 in both groups was similarly high leading to low LBR. Similar fertilization, IR, and CLBR from DOR-Accu and DOR-fresh groups were observed in all age groups. CLBR per OPU was statistically higher in DOR-fresh group and was similarly poor in both groups aged over 40.\u003c/p\u003e\n\u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eClinical outcomes of the strategy for managing DOR according to patient\u0026rsquo;s age compared between fresh M-II oocytes and accumulation of vitrified M-II oocytes\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;35\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e35\u0026ndash;37\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e38\u0026ndash;40\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;40\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAccu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFresh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAccu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFresh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAccu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFresh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAccu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFresh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of OPU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e117\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e192\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e301\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e519\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOPU /patient Mean\u003c/p\u003e\n \u003cp\u003e(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.18\u003c/p\u003e\n \u003cp\u003e(2.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.05 (2.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.28 (2.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.91 (2.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge at ART start (y), mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.89\u003c/p\u003e\n \u003cp\u003e(2.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.86\u003c/p\u003e\n \u003cp\u003e(2.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.954\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.03\u003c/p\u003e\n \u003cp\u003e(0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.09\u003c/p\u003e\n \u003cp\u003e(0.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.696\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.11\u003c/p\u003e\n \u003cp\u003e(0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.84\u003c/p\u003e\n \u003cp\u003e(0.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.17\u003c/p\u003e\n \u003cp\u003e(1.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.36\u003c/p\u003e\n \u003cp\u003e(1.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eM-II oocytes /patient Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.50\u003c/p\u003e\n \u003cp\u003e(3.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.64\u003c/p\u003e\n \u003cp\u003e(1.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.26\u003c/p\u003e\n \u003cp\u003e(5.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.91\u003c/p\u003e\n \u003cp\u003e(1.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.00\u003c/p\u003e\n \u003cp\u003e(4.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.64\u003c/p\u003e\n \u003cp\u003e(1.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.12 (5.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.03\u003c/p\u003e\n \u003cp\u003e(1.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFertilization of fresh survival or M-II % (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.08\u003c/p\u003e\n \u003cp\u003e(22.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.26\u003c/p\u003e\n \u003cp\u003e(24.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.633\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.07\u003c/p\u003e\n \u003cp\u003e(16.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.03\u003c/p\u003e\n \u003cp\u003e(22.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.643\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.51\u003c/p\u003e\n \u003cp\u003e(24.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.85\u003c/p\u003e\n \u003cp\u003e(23.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.936\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.05\u003c/p\u003e\n \u003cp\u003e(20.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.90\u003c/p\u003e\n \u003cp\u003e(28.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.968\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of fresh ET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEmbryos transferred\u003c/p\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.18\u003c/p\u003e\n \u003cp\u003e(0.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.81\u003c/p\u003e\n \u003cp\u003e(0.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.037*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.58\u003c/p\u003e\n \u003cp\u003e(0.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.33\u003c/p\u003e\n \u003cp\u003e(0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.02\u003c/p\u003e\n \u003cp\u003e(0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.27\u003c/p\u003e\n \u003cp\u003e(0.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.33\u003c/p\u003e\n \u003cp\u003e(0.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003cp\u003e(0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePregnancy /ET (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16(44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.481\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(47.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26(47.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16(28.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(31.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.709\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(9.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.239\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImplantation rate %\u003c/p\u003e\n \u003cp\u003e(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.00\u003c/p\u003e\n \u003cp\u003e(39.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.56\u003c/p\u003e\n \u003cp\u003e(38.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.574\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.78\u003c/p\u003e\n \u003cp\u003e(32.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.67\u003c/p\u003e\n \u003cp\u003e(32.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.782\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.28\u003c/p\u003e\n \u003cp\u003e(21.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.43\u003c/p\u003e\n \u003cp\u003e(27.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.471\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.55\u003c/p\u003e\n \u003cp\u003e(10.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.56\u003c/p\u003e\n \u003cp\u003e(16.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.996\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMiscarriage /ET (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.048*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(56.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.011*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(57.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLive birth /ET (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(41.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.279\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(28.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(41.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(12.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19(25.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.735\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of surplus vitrified embryo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurplus vitrified embryo /patient Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.32\u003c/p\u003e\n \u003cp\u003e(1.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003cp\u003e(0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.011*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.24\u003c/p\u003e\n \u003cp\u003e(2.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003cp\u003e(0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.14\u003c/p\u003e\n \u003cp\u003e(1.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003cp\u003e(0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003cp\u003e(1.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003cp\u003e(0.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCumulative live birth /ITT (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(46.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16(44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.874\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(39.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24(43.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.689\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20(27.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.520\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCumulative live birth /OPU (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16(44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24(43.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20(27.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.086\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\"\u003e* \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: Data are mean \u0026plusmn; standard deviation or n (%) and compared among groups using Student\u0026rsquo;s \u003cem\u003et-\u003c/em\u003etest, chi-square test, or Fisher\u0026rsquo;s test\u0026nbsp;for \u003cem\u003eP\u003c/em\u003e-value. Abbreviations: Accu = accumulation of vitrified oocytes; fresh = Fresh oocytes; DOR = diminished ovarian reserve; OPU = ovum pick-up; ART = assisted reproduction technology; M-II = metaphase II; ET = embryo transfer; ITT = intention to treat.\u003c/p\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e showed clinical outcome of patient accumulated vitrified M-II oocytes reach the goal of total number\u0026thinsp;\u0026ge;\u0026thinsp;10 and \u0026ge;\u0026thinsp;15. More mean number of available M-II oocytes to create more embryos for ET in DOR-Accu group contribute to increasing CPR (48.4% vs. 31.0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.054), but it fail to improve LBR per ET (29.0% vs. 26.2%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.738) and CLBR per ITT (29.0% vs. 27.5%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.859). Therefore, higher MR (40.0% vs. 14.1%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03) in DOR-Accu group was still notable.\u003c/p\u003e\n\u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eClinical outcomes of the strategy for managing DOR compared between fresh oocytes and accumulated vitrified oocytes reach\u0026thinsp;\u0026ge;\u0026thinsp;10 or \u0026ge;\u0026thinsp;15 M-II oocytes\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDOR-fresh\u003c/p\u003e\n \u003cp\u003e(A)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDOR-Accu\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;10 M-II (B)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;15 M-II (C)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eA vs B\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eA vs C\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of patient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e229\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of OPU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e229\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e654\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e256\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOPU /patient Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00(0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.54(3.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.26(3.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaternal age at ART start Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.07(3.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.75(3.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.26(3.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAMH Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.72(0.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.57(0.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.67(0.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.376\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eM-II oocytes /patient Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.53(1.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.57(4.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.61(3.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFertilization of fresh and survival egg % (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.29(24.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.88(18.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.31(12.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.215\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.662\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of transfer cycle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e229\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of embryos transferred Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.14(0.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.26(0.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.26(0.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePregnancy /ET (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71(31.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36(36.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(48.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.374\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImplantation rate % (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.47(29.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.08(28.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.34(34.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.861\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMiscarriage /pregnancy (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(14.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(41.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.030*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStill birth /pregnancy (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLive birth /ET (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60(26.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(21.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(29.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.314\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.738\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of surplus vitrified embryo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e179\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurplus vitrified embryo /patient Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.24(0.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.79(2.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.74(2.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCumulative live birth /ITT (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63(27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26(26.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(29.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.777\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.859\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCumulative live birth /OPU (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63(27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26(4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e* \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: Data are mean\u0026nbsp;\u0026plusmn;\u0026nbsp;standard deviation or n (%) and compared among groups using Student\u0026rsquo;s \u003cem\u003et-\u003c/em\u003etest, chi-square test,\u0026nbsp;or Fisher\u0026rsquo;s test\u0026nbsp;for \u003cem\u003eP\u003c/em\u003e-value. Abbreviations: DOR-fresh = diminished ovarian reserve, fresh oocytes; DOR-Accu = diminished ovarian reserve, accumulation of vitrified oocytes; DOR = diminished ovarian reserve; M-II = metaphase II; OPU = ovum pick-up; ART = assisted reproduction technology; AMH = Anti-M\u0026uuml;llerian hormone; ET = embryo transfer; ITT = intention treat.\u003c/p\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e evaluated whether age, AMH, managing DOR strategy, and number of embryos transferred affect clinical outcomes. Although maternal age of ART start and ET were older and AMH was lower in DOR-Accu group compared with DOR-fresh group (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e), it did not affect clinical outcomes. However, a vitrified oocytes accumulation strategy had negative effects on MR per pregnancy (OR: 4.00, 95% CI\u0026thinsp;=\u0026thinsp;1.10\u0026ndash;14.58) and LBR per ET (OR: 0.42, 95% CI\u0026thinsp;=\u0026thinsp;0.20\u0026ndash;0.89). LBR per ET improved as more embryos transfer: 2 embryos (OR: 3.40, 95% CI\u0026thinsp;=\u0026thinsp;1.41\u0026ndash;8.18), 3 embryos (OR: 3.19, 95% CI\u0026thinsp;=\u0026thinsp;1.25\u0026ndash;8.10), and 4 embryos (OR: 5.94, 95% CI\u0026thinsp;=\u0026thinsp;1.99\u0026ndash;17.71).\u003c/p\u003e\n\u003ctable border=\"1\" id=\"Tab4\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe effect of the relevant significant variables on clinical outcomes\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eCPR Adj-OR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMR Adj-OR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLBR Adj-OR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMaternal age at ET\u003csup\u003e✝\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.71 (0.46\u0026ndash;1.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.94 (0.42\u0026ndash;2.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.884\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84 (0.50\u0026ndash;1.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.523\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMaternal age at ART start\u003csup\u003e✝\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.18 (0.77\u0026ndash;1.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e0.448\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.44 (0.65\u0026ndash;3.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.368\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.97 (0.58\u0026ndash;1.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.914\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAMH\u003csup\u003e✝\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.81 (0.41\u0026ndash;1.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e0.561\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78 (0.17\u0026ndash;3.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.739\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.98 (0.44\u0026ndash;2.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.955\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eStrategy\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e0.478\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.036*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.022*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eFresh IVF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAccumulated vitrified M-II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.80 (0.44\u0026ndash;1.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e0.478\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.00 (1.10-14.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.036*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.42 (0.20\u0026ndash;0.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.022*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eNumber of Embryos transferred\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.327\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.013*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.23 (1.80\u0026ndash;9.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.00 (0.00-Inf)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.40 (1.41\u0026ndash;8.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.006*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.48 (2.67\u0026ndash;15.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.00 (0.00-Inf)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.19 (1.25\u0026ndash;8.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.015*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.07 (3.30-24.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.00 (0.00-Inf)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.94 (1.99\u0026ndash;17.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003e* \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003e\u003csup\u003e✝\u003c/sup\u003eContinuous variables\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003e\u003csup\u003e#\u003c/sup\u003eCategorical variables\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003eLinear regression was used to analyze continuous variables and logistic regression was used to evaluate categorical variables. Each variables was adjusted for the strategy for managing DOR, AMH, the number of embryos transferred, ET day, maternal age at ET and ART start. Abbreviations: CPR\u0026thinsp;=\u0026thinsp;clinical pregnancy rate; MR\u0026thinsp;=\u0026thinsp;miscarriage rate; LBR\u0026thinsp;=\u0026thinsp;live birth rate; ET\u0026thinsp;=\u0026thinsp;embryo transfer; ART\u0026thinsp;=\u0026thinsp;assisted reproduction technology; AMH\u0026thinsp;=\u0026thinsp;Anti-M\u0026uuml;llerian hormone; IVF\u0026thinsp;=\u0026thinsp;in vitro fertilization; M-II\u0026thinsp;=\u0026thinsp;metaphase II; ET\u0026thinsp;=\u0026thinsp;embryo transfer.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study showed that DOR women used the vitrified oocytes accumulation strategy to obtain more embryos for transfer fails to improve CPR, and statistically higher MR results in lower LBR per ET. More surplus vitrified embryo did not also improve CLBR.\u003c/p\u003e \u003cp\u003eVitrification-thawing oocytes presented 85.7% survival rate. Based on survival rates of thawing oocytes described in previous studies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11 CR12 CR13\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], we concluded that vitrification-thawing program has been standardized. Vitrified oocytes is a mature technology for reproduction preservation and has similar outcomes to fresh oocytes in donor women [\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. But intracellular ice crystals formation, solution effects, and osmotic shock which cause oocytes damage still exit during cryopreservation. DNA fragmentation, chromosome disorganization, aberrant gene expression, and damage to mitochondria, endoplasmic reticulum, and lysosomes have been also found in oocytes after cryopreservation [\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan additionalcitationids=\"CR36 CR37 CR38 CR39\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Meiotic spindle is determinant of oocyte viability, poor spindle architecture impact chromosome stability, fertilization, and possible embryonic development and results in high aneuploidy levels which cause embryo degeneration and spontaneous abortion [\u003cspan additionalcitationids=\"CR42 CR43 CR44 CR45 CR46\" citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Disappearance and reappearance of the meiotic spindle occur during cooling-thawing procedure, and temperature fluctuations as small as 0.3\u0026deg;C for short times can cause irreversible spindle damage [\u003cspan additionalcitationids=\"CR48 CR49\" citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Aberrant spindles are frequently found in oocytes obtained from women of advanced reproductive age [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e], and it may cause oocytes from older women who are more vulnerable to cryopreservation damage. Our results showed that women aged over 35 in DOR-Accu group has relative high abortion rate compared with DOR-fresh group. It may approve this speculation. Spindle architecture in oocytes from women younger than 35 is healthy and suffers less damage from cooling and thawing. Therefore, MR was comparable to fresh oocytes.\u003c/p\u003e \u003cp\u003eWe set goal of accumulating total number 10\u0026ndash;15 M-II oocytes in DOR-Accu group which was expected to get higher CPR than in fresh oocyte cycle. However, only 100 patients (47.4%) accumulated vitrified oocytes reached total number\u0026thinsp;\u0026ge;\u0026thinsp;10 and 31 patients (14.7%) reached total number\u0026thinsp;\u0026ge;\u0026thinsp;15. This can be attributed to DOR that yielded low oocytes count despite double stimulation in same ovarian cycle maximize oocytes output [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Patients need to receive repeat ovarian stimulation and retrieval 8.26 times to reach total number\u0026thinsp;\u0026ge;\u0026thinsp;15 of accumulation. Although vitrified oocytes accumulation strategy may palliate DOR women the psychological distress that caused by repeated transfer failures [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], they still distress from stimulation cancellation, repeat invasive procedure, and failure retrieving which discourage them from accumulating enough vitrified M-II oocytes. Cost and risk of repeat ovarian stimulation and retrieval could be higher in DOR-Accu group, even in mild COS with flexible gonadotropins use. Even DOR women who accumulate vitrified M-II oocytes reach total number\u0026thinsp;\u0026ge;\u0026thinsp;15 and create more embryos to improve CPR, higher MR (40%) counterbalance it, and result in similar LBR and CLBR per ITT compared with DOR-fresh group. Although, vitrified M-II oocytes need average 6\u0026ndash;9 times of OPU to get similar LBR and CLBR to 1 IVF cycle using fresh oocytes, it is a poorly cost-effective strategy for managing DOR. Previous studies showed vitrified oocytes accumulation strategy inseminated vitrified oocytes that pooled together with fresh oocytes got similar outcomes compared with IVF cycle using fresh oocytes [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. More poor outcomes per ET or per OPU are expected if only accumulated vitrified oocytes were used.\u003c/p\u003e \u003cp\u003eIt is noteworthy that CLBR was poor in both groups as women aged over 40 (8.0% vs. 4.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.52). It is not surprising because previous research reported CLBR from patients who underwent elective fertility preservation worsened dramatically after age of 40 years (3.7%) [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e], and our data showed similar result. In our unpublished data, 14 young women aged\u0026thinsp;\u0026le;\u0026thinsp;37 year who accumulated at least 10 vitrified M-II oocytes could achieve statistically higher CLBR (77.8% vs. 45.8%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015) than DOR-fresh group. CLBR were poor in both group after age of 37 years regardless of number of accumulating vitrified M-II oocytes. Moreover, there were 28 patients who underwent 229 ovum retrievals and harvested 170 oocytes, and these extremely DOR women who obtained less than mean one M-II oocyte per OPU all got no live birth finally. However, we need to extend sample size and performed randomized controlled trial to approve observation results and make conclusion.\u003c/p\u003e \u003cp\u003eOur study has some limitation. It is a retrospective review of patient who had obtained oocytes from retrieval in both groups and we did not include patients who had no embryos transferred for any cause. We did not calculate cycle cancellation rate and patient dropout rate and just focused on transfer outcomes.\u003c/p\u003e \u003cp\u003eIt pointed out that average age at ART start and ET was older, and average AMH serum levels were lower in DOR-Accu group. However, these differences between groups were too minimal to confound clinical outcomes, and it was also approved in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Moreover, statistically higher MR (40.0% vs. 14.1%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03), similar LBR (29.0% vs. 26.2%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.738), and CLBR (29.0% vs. 27.5%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.738) exist in subgroup of patient accumulated vitrified oocytes reach\u0026thinsp;\u0026ge;\u0026thinsp;15 M-II oocytes despite similar age at ART start and AMH serum levels in two groups.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur result demonstrated that accumulation of oocytes by vitrification for DOR women fail to improve LBR even accumulation reach total number\u0026thinsp;\u0026ge;\u0026thinsp;15 vitrified M-II oocytes. Moreover, higher MR (41.4%) in DOR-Accu group resulted in lower LBR (15.2% vs. 26.2%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). It is difficult to accumulate vitrified M-II oocytes to reach total number\u0026thinsp;\u0026ge;\u0026thinsp;15 because only 14.7% achieved the goal. Even if patients reach this goal of accumulating vitrified M-II oocytes, it took average of 8.26 times of OPU to get similar LBR per ET and CLBR to that from 1 IVF cycle using fresh oocytes. Accumulating vitrified M-II oocytes is less efficient and has lower efficacy than IVF cycles using fresh oocytes for managing DOR.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eLive birth rate (LBR), diminished ovarian reserve (DOR), Anti-M\u0026uuml;llerian hormone (AMH), antral follicle count\u0026nbsp;(AFC),\u0026nbsp;diminished\u0026nbsp;ovarian reserve\u0026nbsp;accumulation of vitrified oocytes (DOR-Accu), embryo transfer (ET), \u003cstrong\u003econtrolled ovarian stimulation\u0026nbsp;\u003c/strong\u003e(COS), diminished ovarian reserve fresh oocytes (DOR-fresh), cumulative LBR (CLBR), intention to treat (ITT), clinical pregnancy rate (CPR), miscarriage rate (MR), metaphase II (M-II), Poor ovarian responders (POR), in vitro fertilization (IVF), assisted reproduction technology (ART), gonadotropin-releasing hormone (GnRH), vitrification solution (VS), warming solution (TS), washing solution (WS), intracytoplasmic sperm injection (ICSI), estradiol (E2), implantation rate (IR), odds ratios (OR), confidence intervals (CIs)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by Institutional Review Board of Mackay Memorial Hospital (21MMHIS219e). There is no participants consent for this retrospective study and Institutional Review Board decide this is ethically acceptable. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no external financial support from any commercial company. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eK-S L and R K-K L were involved in the conception and design of the study; K-S L, M-H L, Y-M H and R K-K L were involved in collected patients in MacKay Memorial Hospital; K-S L, J-H Y contributed to data analysis and interpretation; K-S L, M-H L and R K-K L were involved in routine meeting and advising the study design; R K-K L as co-corresponding authors, had the major roles in designing the manuscript, interpreting the analyzed data, advising, drafting, and revising the draft. All authors were involved in the writing of the manuscript and provided final approval. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the medical staff of MacKay Memorial Hospital for involvement and Rufina D for English editing and proofreading in the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eDevine K, Mumford SL, Wu M, DeCherney AH, Hill MJ, Propst A. Diminished ovarian reserve in the United States assisted reproductive technology population: diagnostic trends among 181,536 cycles from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. Fertil Steril 2015; 104:612-9.e3.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAmerican Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve: a committee opinion. 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Limited recovery of meiotic spindles in living human oocytes after cooling-rewarming observed using polarized light microscopy. Hum Reprod. 2001;16(11):2374\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAna Cobo, Juan A Garc\u0026iacute;a-Velasco, Aila Coello, Javier Domingo, Antonio Pellicer, Jos\u0026eacute; Remoh\u0026iacute;. Oocyte vitrification as an efficient option for elective fertility preservation. Fertil Steril 2016;105(3):755\u0026ndash;764.e8.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Diminished ovarian reserve (DOR), fresh oocyte, vitrified oocytes accumulation, live birth rate (LBR)","lastPublishedDoi":"10.21203/rs.3.rs-1482330/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1482330/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Vitrified M-II oocytes accumulation strategy for later simultaneous insemination has been used for managing POR. Our study aimed to determine whether simulation insemination of vitrified oocytes accumulation strategy improves live birth rate (LBR) for managing diminished ovarian reserve (DOR).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u0026nbsp;\u003c/strong\u003eRetrospective study included 440 women with DOR fulfilling Poseidon classification groups 3 and 4, defined as presence of serum anti-Müllerian hormone (AMH) hormone level \u0026lt;1.2 ng/ml or antral follicle count (AFC) \u0026lt;5, from January 1, 2014 to December 31, 2019 in a single department. Patients underwent accumulation of vitrified oocytes (DOR-Accu) and embryo transfer (ET) or controlled ovarian stimulation\u003cstrong\u003e \u003c/strong\u003e(COS) using fresh oocytes\u003cstrong\u003e \u003c/strong\u003e(DOR-fresh) and ET. Primary outcomes were LBR per ET and cumulative LBR (CLBR) per intention to treat (ITT). Secondary outcomes were clinical pregnancy rate (CPR) and miscarriage rate (MR).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u0026nbsp;\u003c/strong\u003e211 patients underwent simultaneous insemination of vitrified oocytes accumulation and ET in DOR-Accu group (maternal age: 39.29 ± 4.23 y, AMH: 0.54 ± 0.35 ng/ml), and 229 patients underwent COS and ET in DOR-fresh group (maternal age: 38.07 ± 3.77 y, AMH: 0.72 ± 0.32 ng/ml). CPR in DOR-Accu group were similar in DOR-fresh group (27.5% vs. 31.0%, \u003cem\u003ep \u003c/em\u003e= 0.418). MR was statistically higher (41.4% vs. 14.1%, \u003cem\u003ep \u003c/em\u003e= 0.001) while LBR per ET was statistically lower (15.2% vs. 26.2%, \u003cem\u003ep \u003c/em\u003e\u0026lt; 0.001) in DOR-Accu group. There is no difference in CLBR per ITT between groups (20.4% vs. 27.5%, \u003cem\u003ep \u003c/em\u003e= 0.081). Clinical outcomes were categorized in four groups with regard to patient’s age in secondary analysis. CPR, LBR per ET, and CLBR did not improved in DOR-Accu group. In group of 31 patients, accumulated vitrified metaphase II (M-II) oocytes reach total number ≥15, CPR improved among DOR-Accu group (48.4% vs. 31.0%, \u003cem\u003ep \u003c/em\u003e= 0.054); however, higher MR (40.0% vs. 14.1%, \u003cem\u003ep \u003c/em\u003e= 0.03) resulted similar LBR per ET (29.0% vs. 26.2%, \u003cem\u003ep \u003c/em\u003e= 0.738).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Vitrified oocytes accumulation for managing DOR did not improve LBR. Higher MR resulted in lower LBR. Vitrified oocytes accumulation strategy for managing DOR is not clinically practical.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTrial registration:\u003c/strong\u003e\u0026nbsp;The study protocol was retrospectively registered and was approved by Institutional Review Board of Mackay Memorial Hospital (21MMHIS219e) on August 26, 2021\u003c/p\u003e","manuscriptTitle":"The Outcomes of Vitrified Oocytes Accumulation for Managing Diminished Ovarian Reserve: A retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-03-28 20:53:56","doi":"10.21203/rs.3.rs-1482330/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a83aa7a7-955a-44cb-ab6b-b6f89d190d66","owner":[],"postedDate":"March 28th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-05-24T12:14:27+00:00","versionOfRecord":[],"versionCreatedAt":"2022-03-28 20:53:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1482330","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1482330","identity":"rs-1482330","version":["v1"]},"buildId":"ehx78VzkSd0WSzXnipQa-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}