Intracytoplasmic sperm injection hampers fertilization rate and pregnancy per initiated cycle in patients with extremely poor ovarian response

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Intracytoplasmic sperm injection (ICSI) in patients with extremely poor ovarian response resulted in a higher total fertilization failure rate and lower cumulative pregnancy rate compared to conventional in vitro fertilization (IVF).

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This retrospective study compared IVF versus ICSI outcomes in 2,572 infertile patients defined as extremely poor responders with only one or two oocytes retrieved (2013–2022), using multivariate regression and propensity score matching to adjust for baseline differences. The ICSI group had a higher total fertilization failure rate than the IVF group, while IVF had a higher multiple fertilization rate; after matching, the cumulative pregnancy rate per initiated cycle was higher with IVF (28.7% vs 21.7%), and the cumulative live birth difference was not statistically significant. A key limitation is that the study is retrospective and preprint-level (not peer reviewed), which may leave residual confounding despite adjustment. Relevance to endometriosis: the paper includes diagnosis of endometriosis as a covariate in propensity score matching and analysis context, though endometriosis is not the main focus of the study.

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Abstract

Abstract Purpose: To compare the clinical outcomes of extremely poor responders with one or two oocytes who receive in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Methods: A retrospective study was carried out in 2572 patients with one or two oocytes retrieved from 2013 to 2022, of which 2159 patients were scheduled to receive IVF treatment and 413 patients were scheduled to receive ICSI treatment. The laboratory parameters and clinical outcomes were compared with adjusted multivariate regression and propensity score (PS) matching. Results: In both matched and non-matched cohorts, the total fertilization failure (TFF) rate of the ICSI group was significantly higher than that of the IVF group (P < 0.05), but the multiple fertilization rate of the IVF group was significantly higher than the ICSI group (P < 0.05). After matching, the cumulative pregnancy rate per initiated cycle in the IVF group was significantly higher than in the ICSI group (28.7% vs 21.7, P=0.028). However, the difference in cumulative live births did not reach significant (21.2 % vs 17.2 %, P =0.179). The adjusted odds ratios for TFF, cumulative pregnancy, and cumulative live birth comparing ICSI versus IVF in multivariate models were 1.65(95%CI: 1.12, 2.43), 0.65(95%CI: 0.46, 0.91), and 0.76(95%CI:0.55, 1.04) respectively. Conclusion: In poor responders with one or two oocytes retrieved, ICSI insemination cannot avoid TFF, and it may hamper the cumulative pregnancy rate.
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Intracytoplasmic sperm injection hampers fertilization rate and pregnancy per initiated cycle in patients with extremely poor ovarian response | 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 Intracytoplasmic sperm injection hampers fertilization rate and pregnancy per initiated cycle in patients with extremely poor ovarian response Jinghua Chen, Lanlan Liu, Zhenfang Liu, Luxiang Pan, Liying Zhou, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5335385/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Apr, 2025 Read the published version in Archives of Gynecology and Obstetrics → Version 1 posted 9 You are reading this latest preprint version Abstract Purpose : To compare the clinical outcomes of extremely poor responders with one or two oocytes who receive in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Methods : A retrospective study was carried out in 2572 patients with one or two oocytes retrieved from 2013 to 2022, of which 2159 patients were scheduled to receive IVF treatment and 413 patients were scheduled to receive ICSI treatment. The laboratory parameters and clinical outcomes were compared with adjusted multivariate regression and propensity score (PS) matching. Results : In both matched and non-matched cohorts, the total fertilization failure (TFF) rate of the ICSI group was significantly higher than that of the IVF group (P < 0.05), but the multiple fertilization rate of the IVF group was significantly higher than the ICSI group (P < 0.05). After matching, the cumulative pregnancy rate per initiated cycle in the IVF group was significantly higher than in the ICSI group (28.7% vs 21.7, P=0.028). However, the difference in cumulative live births did not reach significant (21.2 % vs 17.2 %, P =0.179). The adjusted odds ratios for TFF, cumulative pregnancy, and cumulative live birth comparing ICSI versus IVF in multivariate models were 1.65(95%CI: 1.12, 2.43), 0.65(95%CI: 0.46, 0.91), and 0.76(95%CI:0.55, 1.04) respectively. Conclusion : In poor responders with one or two oocytes retrieved, ICSI insemination cannot avoid TFF, and it may hamper the cumulative pregnancy rate. IVF ICSI Normal fertilization rate Total fertilization failure rate Cumulative live birth rate Poor responder What does this study add to the clinical work The use of ICSI in patients with extremely poor responders is usually driven by fair of total fertilization failure. However, our data suggest that using ICSI in these patients further hampers fertilization. Introduction Since first described in 1992, intracytoplasmic sperm injection (ICSI) has become the gold standard for treating severe male factor infertility in assisted reproductive technologies (ART) [ 1 ]. Nowadays, over half of the ART cycles are inseminated with this technique according to the data of ICMART [ 2 ]. The fact that the number of ICSI cycles outnumbers the ART cycles involving male factor infertility[ 3 ] and varies across geographical regions[ 4 ] suggests that the use of ICSI may be driven by factors beyond male infertility, such as clinic-specific policy [ 5 ] or patients` attitudes[ 6 , 7 ]. Now evidence is clear that using ICSI in non-male factor infertility patients does not improve live birth outcomes [ 8 – 10 ]. The popularity of ICSI is possibly driven by the fear of an expected total fertilization failure during conventional IVF treatment. The fear might be irrational in patients with a normal ovarian response, as the absolute incidence of TFF is rare in the general population[ 11 ]. For patients with only one or two oocytes retrieved, however, the chance of fertilization might be a game of all or none. An intracytoplasmic sperm injection could bypass several pre-fertilization hindrances, confirming the one selected spermatozoon reaches the oocyte, and be deemed as a method to overcome the frustrating TFF[ 12 , 13 ]. However, successful fertilization is not only determined by the entry of the spermatozoon into the oocyte in ICSI cycles [ 14 ]. The developmental competence of the spermatozoon selected by the embryologist could not be guaranteed, as it also bypasses the natural selection barriers. Additionally, mechanical damage to the oocytes is also a potential concern [ 15 ]. Practically, using ICSI in patients with one or two oocytes does not always promise a better fertilization rate. Poorer or equalized fertilization chances were reported along with improved fertilization rates among previous studies comparing ICSI and conventional IVF in patients with one or two oocytes[ 7 , 16 , 17 ]. The heterogeneity could be due to the low statistical power and high patient heterogeneity in such populations. Since a major reason for ICSI overuse is the pressure on the clinicians from the patients` intolerance to TFF, an informed consult would be essential. The present study aimed to provide further evidence concerning the association between ICSI and TFF in patients with one or two oocytes, with a larger sample size and matched indications. In addition, previous evidences were summarized and pooled for further reference. Methods Study Subjects A retrospective study of infertile patients treated at the Reproductive Medicine Center of Xiamen University Affiliated Chenggong Hospital from 2013 to 2022 was included and analyzed. Inclusion criteria were poor responders with one or two oocytes retrieved, patients with a complete cycle where live births had been achieved or no surplus frozen embryos left, and patients with a total motile sperm count (TMC) higher than 2ⅹ10 6 in their male counterparts. Excluded criteria were severe male factor cases, frozen-thawed sperm, and sperm aspiration from the testes or epididymis. The reasons for ICSI in the included patients were borderline or suboptimal semen parameters. Institutional review board approval for this study was obtained from the Ethical Committee of Xiamen University Affiliated Chenggong Hospital. Informed consent was not necessary because this retrospective research was based on non-identifiable records. Laboratory procedures and embryo assessment Oocyte retrieval was performed by transvaginal ultrasound, and oocytes were picked up by a 17 G needle (Cook Medical). Repeated follicular flushing was performed when the oocyte was not retrieved after the initial puncture to maximize chances of recovery. On the same day, semen were collected in sterile containers and were evaluated for sperm density, motility, and morphology according to World Health Organization (WHO) criteria[18]. Sperm was prepared by density gradient centrifugation combined with the upstream method, then it was incubated in an incubator (C200, Labotect) at 37°C, 6% CO2, and 5% O2 in a humidified atmosphere. Consultation and decision-making were carried out following OPU for patents with suboptimal semen parameters. IVF is generally recommended unless the patient insists on ICSI [19]. According to the patient's prior informed consent, the oocytes were assigned to conventional IVF or ICSI. Insemination was performed 4-6 hours after oocyte retrieval, and the sperm concentration was adjusted to 1.5 ~ 3 × 10 5 ml /L for IVF insemination. For ICSI cycles, oocytes were denudated 2 hours following retrieval. Fertilization was judged according to whether the pronucleus appeared at 17 ± 1 h after insemination. Normal fertilization is defined as the observation of two pronuclei (2PN), and multiple pronuclei (MPN) is defined as the presence of ≥ 3 pronuclei. Embryos were cultured in cleavage medium (K-SICM, COOK) on days 1-3 after fertilization, and then in blastocyst medium (K-SIBM, COOK) on days 4-7. To compare the fertilization rate between IVF and ICSI cycles, fertilization rate was defined as fertilized oocyte number/total retrieved oocyte number *100% both in IVF cycles and ICSI cycles. According to the Istanbul Consensus embryo evaluation criteria [20], embryos on day 3 were evaluated. Embryos with very poor morphology arrested embryos, and embryos with all blastomere degenerated or lysed were considered not available. For blastocyst assessment, we used the Gardner grading system [21], The score of high-quality blastocysts was ≥ 4BB. Blastocysts with poor morphological score (≤ CC) or low expansion grade (grade 1-2) were not cryopreservation or transferred. For cryopreservation, a vitrification protocol employing 15% dimethyl sulfoxide, 15% ethylene glycol, and 0.6 M sucrose as cryoprotectants was used for cryopreservation. Embryo transfer was performed using a COOK catheter (COOK, IN, USA) under trans-abdominal ultrasound guidance.14 days after embryo transfer, blood β-HCG level was measured to determine whether pregnancy occurred. Clinical pregnancy was defined by the presence of a gestational sac, and live birth was defined as the live birth of a fetus over 28 weeks of gestation. Cumulative live birth rate (CLBR) and pregnancy refer to the first event taking into account all fresh and frozen transfers from a complete cycle [22]. A complete cycle is defined as a cycle that achieves live birth or all embryo transfer. The secondary outcomes were total fertilization failure, fertilization rate, and multiple pronuclei rate. Statistical analysis For PS matching, the covariates include female age, history of spontaneous miscarriage, parity, OPU order, diagnosis of endometriosis, or polycystic ovary syndrome, the duration of infertility, female BMI, basal FSH, basal LH, AFC, male age, male BMI, sperm normal morphology rate, TMC, ovarian stimulation protocol, gonadotropin starting dose, oocyte yield, and extended culture. After the two groups were matched by the propensity score matching 1:1 ratio with a caliper of 0.2, a Discard of cases was allowed for both case and control. The matching was carried out with a MatchIt package. Standard differences (D) were calculated to evaluate the balance of the distribution of the baseline characteristics between the two groups before and after PS matching using a cobalt package. D < 0.1 was used as the threshold to indicate a negligible difference in the mean or prevalence of a covariate between groups. Multivariate analyses were also carried out in the unmatched and matched cohorts adjusted for the important covariates mentioned above to assess the association between the outcomes (TFF, cumulative pregnancy, CLBR) and insemination protocols. Continuous variables were represented as median [first quartile, third quartile] or median [Min, Max], and mean (SD), while categorical variables are represented as N (percentage). Wilcoxon test was used for continuous variables, and the chi-square test was used for categorical variables. P < 0.05 was considered to be statistically significant. All analyses were based on R software [23]. Results In this study, a total of 2572 patients with fewer than 3 oocytes were analyzed, including 2159 patients receiving IVF and 413 patients receiving ICSI. After PS matching, a total of 401 patients for each group were included in the analysis. The basal characteristics before and after PS matching are shown in Table 1. After matching, the two groups were similar in baseline characteristics. Distributions of the PSs before and after PS matching are shown in Supplementary (Supplementary Figure S1). Table 2 shows the outcomes of the IVF group and ICSI group before and after PS matching. After matching (P > 0.05), the fertilization rate and MPN rate in the IVF group were significantly higher than those in the ICSI group (P < 0.05) in both the matched and unmatched cohorts. On the other hand, the TFF rate in the IVF group was significantly lower than that in the ICSI group(P<0.05). Concerning the cumulative outcomes taking freeze-all cycles into account, the cumulative pregnancy rate in the IVF group was significantly higher than in the ICSI group (P<0.05), although there was no significant difference in the cumulative live birth rate (CLBR)between the two groups (P=0.179) in the matched cohort. Since ICSI is an invasive intervention, we further investigated whether the higher TFF in the ICSI group was due to a difference in oocyte degeneration (Supplementary Table S1). The number of oocytes degenerated was recorded after denudation (D0) and during pronuclei checking (D1) for both ICSI and IVF. However, neither the number of oocytes degenerated nor the proportion of cycles with all oocytes degenerated significantly differed between the two groups. Table 3 shows the results of multivariate analyses for TFF, cumulative pregnancy, and CLBR with adjustment of aforementioned covariates. The details of the models are also shown in (Supplementary Table S2-4). It is shown that ICSI insemination was more likely to lead to the occurrence of TFF, before matching (OR:1.62, 95% CI: 1. 12-2. 33) and after matching (OR: 1. 65; 95% CI: 1.12-2.43). The ICSI group was also associated with a poorer cumulative pregnancy rate (adjusted OR: 0.65; CI: 0.46-0.91). However, the association between insemination protocols and CLBR remained insignificant. To detail the potential effect of other indicators for decision-making of insemination protocols, namely the TMC and maternal age, on the outcomes of interest, we compared the splines where TMC and maternal age were fitted to TFF or CLBR using GAM (Supplementary Figure S2, S3) in the matched cohort. It shows that with the range of TMC evaluated in the study, ICSI appeared to lead to a higher TFF. On the other hand, however, the TFF in IVF patients may increase with increasing maternal age, where ICSI patients are less likely to be affected. IVF patients also appeared to have a higher adjusted CLBR, when TMC <200 million or maternal age between 30 to 40, according to the confidence interval of the splines. To further compare our study with previous evidence, we used the "meta" package to pool the available data on this topic [7,17,24–29]. For both fertilization rates per oocyte and pregnancy per initiated cycle, a high degree of heterogeneity was observed, regardless our data were included or not. However, the pooled effect of the previous study may slightly favor ICSI, if our data were not included (Supplementary Figure S4). Discussion In this study, we focused on infertile couples with extremely poor response and non-severe male factors. The results confirmed that similar canceled ET cycles rate, cycles got no embryo rate, embryo quality, and CLBR were observed between IVF and ICSI, indicating that the insemination method did not affect embryo development ability and pregnancy rate. However, ICSI also led to an increased TFF, suggesting against using ICSI to secure the fertilization of these patients. According to the Vienna Consensus, the TFF of IVF and ICSI cycles should be less than 5%[ 30 ]. However, poor responders may suffer from a much higher incidence of TFF than the general population [ 31 ]. Krog et al. reported that when less than four oocytes were retrieved, the TFF rate increased by three times compared with the normal responders [ 32 ]. A possible reason that drives the increasing use of ICSI is the virtual elimination of cases further complicated by TFF, even though the cumulative evidence did not support the use of the procedure in non-male factor infertile patients[ 33 ]. ICSI grants the consistent ability of a viable spermatozoon to activate an oocyte. However, when the problem is oocyte-origin, even ICSI may fail [ 34 ]. Our previous study also showed that patients with less than four oocytes had an unexpected TFF rate of 21% in their first treatment and semen parameters were not reliable predictors for TFF for these patients [ 11 ]. It might suggest that for poor responders, the problems associated with oocytes are the major detriments to hamper fertilization. One of the most common reasons for TFF is the nucleus-cytoplasmic maturation asynchrony[ 34 ]. Cytoplasmic maturation includes a series of events that are key to oocyte competence, such as the rearrangement of organelles and the accumulation of mRNA, proteins, substrates, and nutrients[ 35 ]. The calcium store content in the endoplasmic reticulum (ER), which is essential for the fertilization event, also increases markedly during maturation, in company with the rearrangement of ER [ 36 ]. Immature cytoplasm may lead to a failed calcium oscillation following fertilization. In this case, even if a single sperm was injected, no sign of fertilization would be observed. For poor responders, the nucleus-cytoplasmic maturation asynchrony might be more frequent due to the possible alternated follicle growth dynamic, abnormal endocrine response, or other stress and anxiety[ 37 ]. The function of cumulus cells surrounding the oocyte which promotes cytoplasm/nucleus maturation through an autocrine/paracrine mechanism may also be impaired in the poor responders [ 38 – 40 ]. Compared with conventional IVF, ICSI requires an earlier denudation, leading to a shorter in vitro incubation of the cumulus-oocyte complex. Several studies have shown that the interval between oocyte retrieval and denudation may affect the outcomes of ICSI [ 41 , 42 ] and some authors suggested that a longer interval might be associated with a better outcome[ 39 , 43 ]. A longer interval may allow the oocytes to reach full maturity with the somatic cell compartment[ 44 , 45 ]. For oocytes with a potential nucleus-cytoplasmic maturation asynchrony problem, such extended culture before insemination might rescue the immaturity. A possible interpretation for the lower TFF in conventional IVF in our cohort may be that a longer denudation interval may partially reserve the synchronized nucleus-cytoplasmic maturation. On the other hand, however, immature or over-mature cytoplasm might also lead to polyspermy when conventional IVF is used [ 46 , 47 ] With conventional IVF, a higher multiple pronuclei (MPN) rate was observed in the cohort. It is generally accepted that MPN formation is due to the abnormal extrusion of the second polar body or to abnormal fertilization with multiple sperm[ 48 ]. With the sign of the extrusion of the second polar body, polyspermy is suspected. Polyspermy could be due to the aging of oocytes or a high number of capitated sperm at the fertilization site [ 46 ]. Practically, these two factors may be additive. The routine sperm concentration for insemination may be fine for oocytes with good competence but lead to polyspermy in oocytes with reduced cortical granule function. Reducing the sperm concentration at the fertilization site with methods such as droplet insemination may be a possible alternative to avoid polyspermy [ 49 ]. Although there have been several previous studies concerning the use of ICSI in patients with low oocyte yield (1–2) and non-sever male infertility[ 7 , 16 , 17 , 24 , 26 – 29 ], considerable heterogeneity was found when comparing these data (Supplementary Figure S4 ). While the majority of the studies [ 16 , 17 , 24 , 26 , 29 ] suggested a fertilization rate favored ICSI, the work of Wu et al., and Sfontouris et al. suggested similar fertilization rates between IVF and ICSI in patients with non-sever male infertility [ 27 , 28 ]. The source of heterogeneity may be from the patients` characteristics or practices of laboratories. Considering the relatively small sample size of these studies [ 7 , 28 ], the confounders may lead to considerable fluctuation of outcomes. As our data have shown, the differences in TFF became diminished when the age of patients increased (Supplementary Figure S2 , S3). On the other hand, however, since the studies were retrospective, inclusion bias may also be considerable. Imbalances in oocyte maturity rates between IVF and ICSI groups were found in several studies [ 24 , 27 , 28 ]. The proportion of MII was usually higher in ICSI patients. For instance, Wang et al. showed a significantly higher MII rate in the ICSI group than in the IVF group in patients with one oocyte and also a higher cumulative live birth rate per cycle [ 24 ]. Since ICSI could only be given to mature oocytes following denudation, it is less clear whether cycles with immature or degenerated oocytes were excluded in these studies. Considering the clinical scenarios, the intention-to-treat inclusion rather than per-protocol inclusion may be more meaningful to the decision-making for patients with very low oocyte yield. The heterogeneity calls for higher-quality evidence on this issue. Our data contribute to the issue by giving evidence in indication-matched, intention-to-treat patients. Similar to fertilization, the reports concerning the effect of ICSI on pregnancy following an initiated cycle in patients with extremely low responses are heterogeneous [ 7 , 17 , 24 – 29 ]. Wang et al. [ 24 ] suggested a cumulative pregnancy rate favoring the ICSI group, which conflicts with our study and Xi et al. [ 29 ]. While low oocyte yield leads to a very limited chance of transfer, earlier studies only reported pregnancies following fresh transfer [ 7 , 17 , 25 – 28 ]. With the increasing use of FET and ovarian stimulation protocols such as the luteal phase stimulation, more recent studies reported cumulative pregnancy or live birth following a complete cycle. Considering the cumulative chance of pregnancy, the latest evidence in normal responders with non-severy infertility has implied that outcomes following complete cycles would be hampered by the ICSI procedure[ 50 ]. A similar effect would be expected in patients with very low oocyte yield, although the small sample size, low number of events, and high uncertainty are also expected in these patients. Strength and limitations In comparison with previous studies, the strength of the study may include a larger sample size, adjustment for a set of covariates using PS matching, and the reporting of the cumulative outcomes per complete cycle. However, the study is also limited by the retrospective design. In addition, due to the low reproductive potential of poor responders, the current sample size may lack sufficient power to detect the difference in CLBR between the groups while the confidence interval may suggest a trend favoring IVF. Considering that the latest level 1 evidence suggested that ICSI may slightly decrease the CLBR in patients with an adjusted risk ratio of 0.89 [ 50 ], a similar difference would be expected in poor responders with a larger sample size. Conclusion Our data show that for poor responders with only one or two oocytes retrieved, ICSI cannot avoid TFF. Alternatively, it reduces fertilization and cumulative pregnancy rates. It is suggested that ICSI is not a good choice for extremely poor responders even for securing fertilization. Furthermore, the technical complexity, the cost, the potential damage to oocytes, and possible long-term health issues are also potential concerns of this invasive technique [ 15 , 33 , 50 ]. Declarations Author Contribution Jinghua Chen, Jiali Cai, and Jianzhi Ren contribute to conception and design. Zhengfang Liu, Jinghua Chen, Kaijie Chen, Xiaolian Yang and Liying Zhou contribute to the acquisition of data. Jinghua Chen, Lanlan Liu, Jiali Cai, Yurong Chen and Xiaolian Yang contribute to the analysis and interpretation of data. All authors contributed to drafting the article or revising it critically for important intellectual content. All authors read and approved the final manuscript. Acknowledgement We thank Xinli Wang for her assistance in the data processing. This work was supported by the National Natural Science Foundation of China [grant number 22176159]; the Xiamen Medical Advantage subspecialty construction project [grant number 2018296] and the Wu Jieping Medical Foundation [grant number 320.6750.2024-6-14]. References Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. 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Prediction of Fertilization Disorders in the In Vitro Fertilization/Intracytoplasmic Sperm Injection: A Retrospective Study of 106,728 Treatment Cycles. Frontiers in Endocrinology [Internet]. 2022 [cited 2024 Aug 6];13. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065263/ Krog M, Prior M, Carlsen E, Loft A, Forman J, Pinborg A, et al. Fertilization failure after IVF in 304 couples–a case-control study on predictors and long-term prognosis. Eur J Obstet Gynecol Reprod Biol. 2015;184:32–7. Bosch E, Espinós JJ, Fabregues F, Fontes J, García-Velasco J, Llácer J, et al. ALWAYS ICSI? A SWOT analysis. J Assist Reprod Genet. 2020;37:2081–92. Neri QV, Lee B, Rosenwaks Z, Machaca K, Palermo GD. Understanding fertilization through intracytoplasmic sperm injection (ICSI). Cell Calcium. 2014;55:24–37. Watson AJ. Oocyte cytoplasmic maturation: a key mediator of oocyte and embryo developmental competence. J Anim Sci. 2007;85:E1-3. Wakai T, Mehregan A, Fissore RA. Ca2 + Signaling and Homeostasis in Mammalian Oocytes and Eggs. Cold Spring Harb Perspect Biol. 2019;11:a035162. Gonda KJ, Domar AD, Gleicher N, Marrs RP. Insights from clinical experience in treating IVF poor responders. Reprod Biomed Online. 2018;36:12–9. Johnson JE, Higdon HL, Boone WR. Effect of human granulosa cell co-culture using standard culture media on the maturation and fertilization potential of immature human oocytes. Fertil Steril. 2008;90:1674–9. Lu X, Lv X, Dong X, Li Y, Turathum B, Liu S, et al. Increased serine synthesis in cumulus cells of young infertile women with diminished ovarian reserve. Human Reproduction. 2023;38:1723–32. Del Bianco D, Gentile R, Sallicandro L, Biagini A, Quellari PT, Gliozheni E, et al. Electro-Metabolic Coupling of Cumulus-Oocyte Complex. Int J Mol Sci. 2024;25:5349. Patrat C, Kaffel A, Delaroche L, Guibert J, Jouannet P, Epelboin S, et al. Optimal timing for oocyte denudation and intracytoplasmic sperm injection. 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How does polyspermy happen in mammalian oocytes? Microsc Res Tech. 2003;61:335–41. van der Ven HH, Al-Hasani S, Diedrich K, Hamerich U, Lehmann F, Krebs D. Polyspermy in in vitro fertilization of human oocytes: frequency and possible causes. Ann N Y Acad Sci. 1985;442:88–95. Kemper JM, Liu Y, Afnan M, Mol BWJ, Morbeck DE. What happens to abnormally fertilized embryos? A scoping review. Reprod Biomed Online. 2023;46:802–7. Microdroplet in vitro fertilization can reduce the number of spermatozoa necessary for fertilizing oocytes - PubMed [Internet]. [cited 2024 Aug 5]. Available from: https://pubmed.ncbi.nlm.nih.gov/24583808/ Wang Y, Li R, Yang R, Zheng D, Zeng L, Lian Y, et al. Intracytoplasmic sperm injection versus conventional in-vitro fertilisation for couples with infertility with non-severe male factor: a multicentre, open-label, randomised controlled trial. Lancet. 2024;S0140-6736(23)02416-9. Tables Table 1. Basic characteristics before and after PS matching for OPU cycles Variables Before Matching After Matching IVF ICSI D* IVF ICSI D* (N=2159) (N=413) (N=401) (N=401) Female age, year 35.0[31.0,39.0] 36.0[32.0,39.0] 0.1149 36.0[32.0,40.0] 36.0[32.0,39.0] -0.0021 History of spontaneous miscarriage ( % ) 0 1790 (82.9%) 344 (83.3%) 0.0038 333 (83.0%) 334 (83.3%) 0.0025 1 303 (14.0%) 58 (14.0%) 0.0001 60 (15.0%) 56 (14.0%) -0.01 2 45 (2.1%) 6 (1.5%) -0.006 3 (0.7%) 6 (1.5%) 0.0075 ≧3 21 (1.0%) 5 (1.2%) 0.0024 5 (1.2%) 5 (1.2%) 0 Parity ≧ 1 (%) 686 (31.8%) 123 (29.8%) -0.02 121 (30.2%) 121 (30.2%) 0 OPU order ( % ) 1 1347 (62.4%) 95 (23.0%) -0.394 88 (21.9%) 95 (23.7%) 0.0175 2 521 (24.1%) 176 (42.6%) 0.1848 188 (46.9%) 173 (43.1%) -0.0374 ≧3 291 (13.5%) 142 (34.4%) 0.209 125 (31.2%) 133 (33.2%) 0.02 Endometriosis (%) 282 (13.1%) 47 (11.4%) -0.017 51 (12.7%) 47 (11.7%) -0.01 PCOs (%) 45 (2.1%) 13 (3.1%) 0.0106 12 (3.0%) 11 (2.7%) -0.0025 Duration of infertility, year 3.90[2.00,6.00] 5.00[2.70,7.50] 0.2343 4.40[2.00,8.00] 4.80[2.60,7.50] -0.0423 Female BMI, kg/cm 2 21.8[20.1,23.2] 22.0[20.0,23.1] 0.0104 21.9[20.3,23.2] 21.9[20.0,23.1] -0.0267 Basal FSH, IU/l 8.90 [0.40, 1210] 9.32 [1.88, 698] 0.0386 9.17 [2.31, 34.9] 9.32 [1.88, 35.0] -0.0024 Basal LH, IU/l 3.85 [0.01, 30.7] 3.78 [0.880, 62.6] -0.007 3.80 [0.12, 30.4] 3.75 [0.88, 62.6] -0.0025 Antral follicle count 5.00[3.00,7.00] 5.00[3.00,7.00] -0.021 5.00[3.00,7.00] 5.00[3.00,7.00] -0.0199 Male age, year 36.0[32.0,40.0] 37.0[33.0,41.0] 0.1337 37.0[33.0,41.0] 37.0[33.0,41.0] -0.0152 Male BMI, kg/cm 2 23.9[21.8,25.9] 23.9[21.9,26.0] -0.0001 23.9[21.6,26.0] 24.0[21.9,26.0] 0.0196 Sperm normal morphology rate (%) 6.00[4.00,9.00] 4.50[3.00,8.00] -0.132 5.00[3.50,8.00] 4.80[3.00,8.00] 0.0205 Total motile sperm number ( x10 6 ) 55.9[28.3,100] 27.6[8.34,63.0] -0.572 37.6[20.0,67.0] 29.2[8.39,63.2] -0.0742 Ovarian stimulation protocols (%) Luteal phase 87 (4.0%) 35 (8.5%) 0.0444 36 (9.0%) 31 (7.7%) -0.0125 Mild stimulation 128 (5.9%) 21 (5.1%) -0.008 20 (5.0%) 21 (5.2%) 0.0025 GnRH antagonist 1029 (47.7%) 179 (43.3%) -0.043 183 (45.6%) 177 (44.1%) -0.015 GnRH agonist 725 (33.6%) 138 (33.4%) -0.002 135 (33.7%) 133 (33.2%) -0.005 Other protocols 12 (0.6%) 3 (0.7%) 0.0017 2 (0.5%) 3 (0.7%) 0.0025 Natural cycle 178 (8.2%) 37 (9.0%) 0.0071 25 (6.2%) 36 (9.0%) 0.0274 GN starting dose, IU 225 [0, 300] 225 [0, 300] -0.076 225 [0, 300] 225 [0, 300] -0.088 Oocyte yield 0.0447 -0.0175 1 980 (45.4%) 169 (40.9%) 161 (40.1%) 168 (41.9%) 2 1179 (54.6%) 244 (59.1%) 240 (59.9%) 233 (58.1%) Extended culture (%) 118 (5.5%) 32 (7.7%) 0.0228 26 (6.5%) 31 (7.7%) 0.0125 Data were presented as Median [first quartile, third quartile] and mean (SD) for continuous variables and n (percentage) for categorical variables. *D: Standardized difference. The absolute value of D is less than 0.1, cohorts can be considered to be balanced with respect to the demographics being assessed. OPU, oocyte pick up; PCOs, polycystic ovarian syndrome; BMI, body mass index; FSH, follicle-stimulating hormone; LH, luteinizing hormone; GnRH, gonadotropin; GN, gonadotropin. Table 2. Clinical outcomes before and after PS matching for OPU cycles Before Matching After Matching Variables IVF ICSI P-value IVF ICSI P-value (N=2159) (N=413) (N=401) (N=401) Canceled ET cycles (%) 744 (34.5%) 165 (40.0%) 0.0373 142 (35.4%) 157 (39.2%) 0.307 Cycles got no embryo (%) 577 (26.7%) 117 (28.3%) 0.54 101 (25.2%) 114 (28.4%) 0.339 Freeze-all cycle (%) 167 (7.7%) 48 (11.6%) 0.0118 41 (10.2%) 43 (10.7%) 0.908 TFF cycle (%) 187 (8.7%) 58 (14.0%) <0.001 31 (7.7%) 56 (14.0%) 0.00643 Mature oocyte number Mean (SD) 1.42 (0.582) 1.45 (0.575) 0.258 1.47 (0.592) 1.44 (0.577) 0.375 Median [Min, Max] 1.00 [0, 2.00] 1.00 [0, 2.00] 2.00 [0, 2.00] 1.00 [0, 2.00] Fertilization rate, (%) Mean (SD) 85.7 (30.7) 76.0 (36.5) <0.001 86.8 (29.6) 76.1 (36.4) <0.001 Median [Min, Max] 100 [0, 100] 100 [0, 100] 100 [0, 100] 100 [0, 100] MPN rate, (%) Mean (SD) 20.80 (42.70) 5.33 (22.50) <0.001 20.00 (42.40) 5.24 (22.30) <0.001 Median [Min, Max] 0 [0, 100.00] 0 [0, 100.00] 0 [0, 100.00] 0 [0, 100.00] Normal fertilization rate, (%) Mean (SD) 64.2 (41.6) 67.7 (40.8) 0.114 65.7 (40.5) 67.6 (40.9) 0.426 Median [Min, Max] 100 [0, 100] 100 [0, 100] 100 [0, 100] 100 [0, 100] Cleavage 2PN embryo rate, (%) Mean (SD) 73.9 (43.6) 77.1 (41.8) 0.158 76.2 (42.3) 76.9 (42.0) 0.769 Median [Min, Max] 100 [0, 100] 100 [0, 100] 100 [0, 100] 100 [0, 100] Available embryo number Mean (SD) 0.722 (0.737) 0.826 (0.766) 0.0118 0.800 (0.768) 0.813 (0.760) 0.787 Median [Min, Max] 1.00 [0, 2.00] 1.00 [0, 2.00] 1.00 [0, 2.00] 1.00 [0, 2.00] High-quality embryo rate, ( % ) Mean (SD) 37.2 (46.4) 38.4 (45.9) 0.537 40.4 (46.9) 38.4 (46.1) 0.575 Median [Min, Max] 0 [0, 100] 0 [0, 100] 0 [0, 100] 0 [0, 100] Cumulative pregnancy, (%) 563 (26.1%) 90 (21.8%) 0.0765 115 (28.7%) 87 (21.7%) 0.0281 CLB rate, (%) 444 (20.6%) 72 (17.4%) 0.165 85 (21.2%) 69 (17.2%) 0.179 Data were presented as mean (SD) and median [Min, Max] for continuous variables and n (percentage) for categorical variables. TFF, total fertilization failure; PN, pronuclei; MPN, multi pronuclei; CLB, cumulative live birth. Table 3. Association between insemination protocols and outcomes in patients with one or two oocyte Characteristic Before Matching p-value After Matching p-value OR 1 95% CI 1 OR 1 95% CI 1 Total fertilization failure IVF ref ref ref ref ICSI 1.62 1.12, 2.33 0.009 1.65 1.12, 2.43 0.011 Cumulative pregnancy IVF ref ref ref ref ICSI 0.77 0.58, 1.02 0.071 0.65 0.46, 0.91 0.013 Cumulative live birth IVF ref ref ref ref ICSI 0.82 0.60, 1.11 0.2 0.76 0.55, 1.04 0.094 1 OR = Odds Ratio, CI = Confidence Interval Models were adjusted for female age, female BMI, female basal FSH, LH, AFC, previous maternal history, PCOS, endometriosis, OPU order, male BMI, male age, sperm normal morphology rate, total motile sperm number, stimulation protocol, oocyte yield and extended culture . Additional Declarations No competing interests reported. Supplementary Files FigureS1.jpg Figure S1. Distribution of propensity scores (distance) before and after matching FigureS2.tiff Figure S2.Change of cycle outcomes across TMC levels in different insemination protocols. (A) Crude TFF across TMC levels in different insemination protocols. (B) Adjusted TFF across TMC levels in different insemination protocols; (C) Crude cumulative live birth across TMC levels in different insemination protocols. (D) Adjusted cumulative live births across TMC levels in different insemination protocols. Models were adjusted for female age, female BMI, female basal FSH, LH, AFC, previous maternal history, PCOS, endometriosis, OPU order, male BMI, male age, sperm normal morphology rate, total motile sperm number, stimulation protocol, oocyte yield and extended culture in GAM models. FigureS3.tiff Figure S3.Change of cycle outcomes across MATERNAL AGE levels in different insemination protocols. (A) Crude TFF across MATERNAL AGE levels in different insemination protocols. (B) Adjusted TFF across MATERNAL AGE levels in different insemination protocols; (C) Crude cumulative live birth across MATERNAL AGE levels in different insemination protocols. (D) Adjusted cumulative live births across MATERNAL AGE levels in different insemination protocols. Models were adjusted for female age, female BMI, female basal FSH, LH, AFC, previous maternal history, PCOS, endometriosis, OPU order, male BMI, male age, sperm normal morphology rate, total motile sperm number, stimulation protocol, oocyte yield and extended culture in GAM models. FigureS4.jpg Supplementary Figure S4. Pooled analysis of existing evidence of the effect of ICSI on patients with 1-2 oocytes. (A) Pooled analysis of the evidence before our study concerning the fertilization rate in patients with 1-2 oocytes; (B) Pooled analysis of the evidence including our study concerning the fertilization rate in patients with 1-2 oocytes; (C) Pooled analysis of the evidence before our study concerning the pregnancy per cycle in patients with 1-2 oocytes; (D) Pooled analysis of the evidence including our study concerning the pregnancy per cycle in patients with 1-2 oocytes. supplementaryTables.docx Cite Share Download PDF Status: Published Journal Publication published 30 Apr, 2025 Read the published version in Archives of Gynecology and Obstetrics → Version 1 posted Editorial decision: Revision requested 17 Feb, 2025 Reviews received at journal 17 Feb, 2025 Reviews received at journal 04 Feb, 2025 Reviewers agreed at journal 15 Jan, 2025 Reviewers agreed at journal 13 Jan, 2025 Reviewers invited by journal 11 Dec, 2024 Editor assigned by journal 27 Oct, 2024 Submission checks completed at journal 26 Oct, 2024 First submitted to journal 25 Oct, 2024 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. 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09:48:14","extension":"tiff","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":22316394,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure S2\u003c/strong\u003e.Change of cycle outcomes across TMC levels in different insemination protocols.\u003c/p\u003e\n\u003cp\u003e(A) Crude TFF across TMC levels in different insemination protocols. (B) Adjusted TFF across TMC levels in different insemination protocols; (C) Crude cumulative live birth across TMC levels in different insemination protocols. (D) Adjusted cumulative live births across TMC levels in different insemination protocols. Models were adjusted for female age, female BMI, female basal FSH, LH, AFC, previous maternal history, PCOS, endometriosis, OPU order, male BMI, male age, sperm normal morphology rate, total motile sperm number, stimulation protocol, oocyte yield and extended culture in GAM models.\u003c/p\u003e","description":"","filename":"FigureS2.tiff","url":"https://assets-eu.researchsquare.com/files/rs-5335385/v1/be020b916723b1d12f0be115.tiff"},{"id":68346275,"identity":"03ca3705-f7ec-4cfc-a61b-49e842820a20","added_by":"auto","created_at":"2024-11-06 09:48:14","extension":"tiff","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":22316394,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure S3.\u003c/strong\u003eChange of cycle outcomes across MATERNAL AGE levels in different insemination protocols.\u003c/p\u003e\n\u003cp\u003e(A) Crude TFF across MATERNAL AGE levels in different insemination protocols. (B) Adjusted TFF across MATERNAL AGE levels in different insemination protocols; (C) Crude cumulative live birth across MATERNAL AGE levels in different insemination protocols. (D) Adjusted cumulative live births across MATERNAL AGE levels in different insemination protocols. Models were adjusted for female age, female BMI, female basal FSH, LH, AFC, previous maternal history, PCOS, endometriosis, OPU order, male BMI, male age, sperm normal morphology rate, total motile sperm number, stimulation protocol, oocyte yield and extended culture in GAM models.\u003c/p\u003e","description":"","filename":"FigureS3.tiff","url":"https://assets-eu.researchsquare.com/files/rs-5335385/v1/c4aa8af70365748235779ebc.tiff"},{"id":68346277,"identity":"c83cfd8f-2e16-4121-a68a-f22279a849e1","added_by":"auto","created_at":"2024-11-06 09:48:14","extension":"jpg","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":326658,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Figure S4.\u003c/strong\u003e Pooled analysis of existing evidence of the effect of ICSI on patients with 1-2 oocytes.\u003c/p\u003e\n\u003cp\u003e(A) Pooled analysis of the evidence before our study concerning the fertilization rate in patients with 1-2 oocytes; (B) Pooled analysis of the evidence including our study concerning the fertilization rate in patients with 1-2 oocytes; (C) Pooled analysis of the evidence before our study concerning the pregnancy per cycle in patients with 1-2 oocytes; (D) Pooled analysis of the evidence including our study concerning the pregnancy per cycle in patients with 1-2 oocytes.\u003c/p\u003e","description":"","filename":"FigureS4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5335385/v1/7007e12b82579928b16c55c3.jpg"},{"id":68346276,"identity":"de306287-6c58-4379-9bb5-2654ce3d1089","added_by":"auto","created_at":"2024-11-06 09:48:14","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":29216,"visible":true,"origin":"","legend":"","description":"","filename":"supplementaryTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-5335385/v1/35f469cf3a36c7af5c0963dc.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Intracytoplasmic sperm injection hampers fertilization rate and pregnancy per initiated cycle in patients with extremely poor ovarian response","fulltext":[{"header":"What does this study add to the clinical work","content":"\u003cp\u003eThe use of \u0026nbsp;ICSI in patients with extremely poor responders is usually driven by fair of total fertilization failure. However, our data suggest that using ICSI in these patients further hampers fertilization.\u0026nbsp;\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eSince first described in 1992, intracytoplasmic sperm injection (ICSI) has become the gold standard for treating severe male factor infertility in assisted reproductive technologies (ART) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Nowadays, over half of the ART cycles are inseminated with this technique according to the data of ICMART [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The fact that the number of ICSI cycles outnumbers the ART cycles involving male factor infertility[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] and varies across geographical regions[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] suggests that the use of ICSI may be driven by factors beyond male infertility, such as clinic-specific policy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] or patients` attitudes[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNow evidence is clear that using ICSI in non-male factor infertility patients does not improve live birth outcomes [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The popularity of ICSI is possibly driven by the fear of an expected total fertilization failure during conventional IVF treatment. The fear might be irrational in patients with a normal ovarian response, as the absolute incidence of TFF is rare in the general population[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. For patients with only one or two oocytes retrieved, however, the chance of fertilization might be a game of all or none. An intracytoplasmic sperm injection could bypass several pre-fertilization hindrances, confirming the one selected spermatozoon reaches the oocyte, and be deemed as a method to overcome the frustrating TFF[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, successful fertilization is not only determined by the entry of the spermatozoon into the oocyte in ICSI cycles [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The developmental competence of the spermatozoon selected by the embryologist could not be guaranteed, as it also bypasses the natural selection barriers. Additionally, mechanical damage to the oocytes is also a potential concern [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePractically, using ICSI in patients with one or two oocytes does not always promise a better fertilization rate. Poorer or equalized fertilization chances were reported along with improved fertilization rates among previous studies comparing ICSI and conventional IVF in patients with one or two oocytes[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The heterogeneity could be due to the low statistical power and high patient heterogeneity in such populations. Since a major reason for ICSI overuse is the pressure on the clinicians from the patients` intolerance to TFF, an informed consult would be essential. The present study aimed to provide further evidence concerning the association between ICSI and TFF in patients with one or two oocytes, with a larger sample size and matched indications. In addition, previous evidences were summarized and pooled for further reference.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Subjects\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA retrospective study of infertile patients treated at the Reproductive Medicine Center of Xiamen University Affiliated Chenggong Hospital from 2013 to 2022 was included and analyzed. Inclusion criteria were poor responders with one or two oocytes retrieved, patients with a complete cycle where live births had been achieved or no surplus frozen embryos left, and patients with a total motile sperm count (TMC) higher than 2ⅹ10\u003csup\u003e6\u003c/sup\u003e in their male counterparts. Excluded criteria were severe male factor cases, frozen-thawed sperm, and sperm aspiration from the testes or epididymis. The reasons for ICSI in the included patients were borderline or suboptimal semen parameters.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInstitutional review board approval for this study was obtained from the Ethical Committee of Xiamen University Affiliated Chenggong Hospital. Informed consent was not necessary because this retrospective research was based on non-identifiable records.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLaboratory procedures and embryo assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOocyte retrieval was performed by transvaginal ultrasound, and oocytes were picked up by a 17 G needle (Cook Medical). Repeated follicular flushing was performed when the oocyte was not retrieved after the initial puncture to maximize chances of recovery. On the same day, semen were collected in sterile containers and were evaluated for sperm density, motility, and morphology according to World Health Organization (WHO) criteria[18]. Sperm was prepared by density gradient centrifugation combined with the upstream method, then it was incubated in an incubator (C200, Labotect) at 37\u0026deg;C, 6% CO2, and 5% O2 in a humidified atmosphere.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsultation and decision-making were carried out following OPU for patents with suboptimal semen parameters. IVF is generally recommended unless the patient insists on ICSI\u0026nbsp;[19]. According to the patient\u0026apos;s prior informed consent, the oocytes were assigned to conventional IVF or ICSI. Insemination was performed 4-6 hours after oocyte retrieval, and the sperm concentration was adjusted to 1.5 ~ 3 \u0026times; 10\u003csup\u003e5\u003c/sup\u003eml /L for IVF insemination. For ICSI cycles, oocytes were denudated 2 hours following retrieval.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFertilization was judged according to whether the pronucleus appeared at 17 \u0026plusmn; 1 h after insemination. Normal fertilization is defined as the observation of two pronuclei (2PN), and multiple pronuclei (MPN) is defined as the presence of \u0026ge; 3 pronuclei. Embryos were cultured in cleavage medium (K-SICM, COOK) on days 1-3 after fertilization, and then in blastocyst medium (K-SIBM, COOK) on days 4-7. To compare the fertilization rate between IVF and ICSI cycles, fertilization rate was defined as fertilized oocyte number/total retrieved oocyte number *100% both in IVF cycles and ICSI cycles. According to the Istanbul Consensus embryo evaluation criteria\u0026nbsp;[20], embryos on day 3 were evaluated. Embryos with very poor morphology arrested embryos, and embryos with all blastomere degenerated or lysed were considered not available. For blastocyst assessment, we used the Gardner grading system\u0026nbsp;[21], The score of high-quality blastocysts was \u0026ge; 4BB. Blastocysts with poor morphological score (\u0026le; CC) or low expansion grade (grade 1-2) were not cryopreservation or transferred. For cryopreservation, a vitrification protocol employing 15% dimethyl sulfoxide, 15% ethylene glycol, and 0.6 M sucrose as cryoprotectants was used for cryopreservation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEmbryo transfer was performed using a COOK catheter (COOK, IN, USA) under trans-abdominal ultrasound guidance.14 days after embryo transfer, blood \u0026beta;-HCG level was measured to determine whether pregnancy occurred. Clinical pregnancy was defined by the presence of a gestational sac, and live birth was defined as the live birth of a fetus over 28 weeks of gestation.\u0026nbsp;Cumulative live birth rate (CLBR) and pregnancy refer to the first event taking into account all fresh and frozen transfers from a complete cycle\u0026nbsp;[22]. A complete cycle is defined as a cycle that achieves live birth or all embryo transfer. The secondary outcomes were total fertilization failure, fertilization rate, and multiple pronuclei rate.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor PS matching, the covariates include female age, history of spontaneous miscarriage, parity, OPU order, diagnosis of endometriosis, or polycystic ovary syndrome, the duration of infertility, female BMI, basal FSH, basal LH, AFC, male age, male BMI, sperm normal morphology rate, TMC, ovarian stimulation protocol, gonadotropin starting dose, oocyte yield, and extended culture. After the two groups were matched by the propensity score matching 1:1 ratio with a caliper of 0.2, a Discard of cases was allowed for both case and control. The matching was carried out with a MatchIt package.\u003c/p\u003e\n\u003cp\u003eStandard differences (D) were calculated to evaluate the balance of the distribution of the baseline characteristics between the two groups before and after PS matching using a cobalt package. D \u0026lt; 0.1 was used as the threshold to indicate a negligible difference in the mean or prevalence of a covariate between groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMultivariate analyses were also carried out in the unmatched and matched cohorts adjusted for the important covariates mentioned above to assess the association between the outcomes (TFF, cumulative pregnancy, CLBR) and insemination protocols.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eContinuous variables were represented as median [first quartile, third quartile] or median [Min, Max], and mean (SD), while categorical variables are represented as N (percentage). Wilcoxon test was used for continuous variables, and the chi-square test was used for categorical variables. P \u0026lt; 0.05 was considered to be statistically significant.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll analyses were based on R software [23].\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eIn this study, a total of 2572 patients with fewer than 3 oocytes were analyzed, including 2159 patients receiving IVF and 413 patients receiving ICSI. After PS matching, a total of 401 patients for each group were included in the analysis. The basal characteristics before and after PS matching are shown in Table 1. After matching, the two groups were similar in baseline characteristics. Distributions of the PSs before and after PS matching are shown in Supplementary (Supplementary Figure S1).\u003c/p\u003e\n\u003cp\u003eTable 2 shows the outcomes of the IVF group and ICSI group before and after PS matching. After matching (P \u0026gt; 0.05), the fertilization rate and MPN rate in the IVF group were significantly higher than those in the ICSI group (P \u0026lt; 0.05) in both the matched and unmatched cohorts. On the other hand, the TFF rate in the IVF group was significantly lower than that in the ICSI group(P\u0026lt;0.05). Concerning the cumulative outcomes taking freeze-all cycles into account, the cumulative pregnancy rate in the IVF group was significantly higher than in the ICSI group (P\u0026lt;0.05), although there was no significant difference in the cumulative live birth rate\u0026nbsp;(CLBR)between the two groups (P=0.179) in the matched cohort.\u003c/p\u003e\n\u003cp\u003eSince ICSI is an invasive intervention, we further investigated whether the higher TFF in the ICSI group was due to a difference in oocyte degeneration (Supplementary Table S1). The number of oocytes degenerated was recorded after denudation (D0) and during pronuclei checking (D1) for both ICSI and IVF. However, neither the number of oocytes degenerated nor the proportion of cycles with all oocytes degenerated significantly differed between the two groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3 shows the results of multivariate analyses for TFF, cumulative pregnancy, and CLBR with adjustment of aforementioned covariates. The details of the models are also shown in (Supplementary Table S2-4). It is shown that ICSI insemination was more likely to lead to the occurrence of TFF, before matching (OR:1.62, 95% CI: 1. 12-2. 33) and after matching (OR: 1. 65; 95% CI: 1.12-2.43). The ICSI group was also associated with a poorer cumulative pregnancy rate (adjusted OR: 0.65; CI: 0.46-0.91). However, the association between insemination protocols and CLBR remained insignificant.\u003c/p\u003e\n\u003cp\u003eTo detail the potential effect of other indicators for decision-making of insemination protocols, namely the TMC and maternal age, on the outcomes of interest, we compared the splines where TMC and maternal age were fitted to TFF or CLBR using GAM (Supplementary Figure S2, S3) in the matched cohort. It shows that with the range of TMC evaluated in the study, ICSI appeared to lead to a higher TFF. On the other hand, however, the TFF in IVF patients may increase with increasing maternal age, where ICSI patients are less likely to be affected. IVF patients also appeared to have a higher adjusted CLBR, when TMC \u0026lt;200 million or maternal age between 30 to 40, according to the confidence interval of the splines.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo further compare our study with previous evidence, we used the \u0026quot;meta\u0026quot; package to pool the available data on this topic [7,17,24\u0026ndash;29]. For both fertilization rates per oocyte and pregnancy per initiated cycle, a high degree of heterogeneity was observed, regardless our data were included or not. However, the pooled effect of the previous study may slightly favor ICSI, if our data were not included (Supplementary Figure S4).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we focused on infertile couples with extremely poor response and non-severe male factors. The results confirmed that similar canceled ET cycles rate, cycles got no embryo rate, embryo quality, and CLBR were observed between IVF and ICSI, indicating that the insemination method did not affect embryo development ability and pregnancy rate. However, ICSI also led to an increased TFF, suggesting against using ICSI to secure the fertilization of these patients.\u003c/p\u003e \u003cp\u003eAccording to the Vienna Consensus, the TFF of IVF and ICSI cycles should be less than 5%[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. However, poor responders may suffer from a much higher incidence of TFF than the general population [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Krog et al. reported that when less than four oocytes were retrieved, the TFF rate increased by three times compared with the normal responders [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. A possible reason that drives the increasing use of ICSI is the virtual elimination of cases further complicated by TFF, even though the cumulative evidence did not support the use of the procedure in non-male factor infertile patients[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. ICSI grants the consistent ability of a viable spermatozoon to activate an oocyte. However, when the problem is oocyte-origin, even ICSI may fail [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Our previous study also showed that patients with less than four oocytes had an unexpected TFF rate of 21% in their first treatment and semen parameters were not reliable predictors for TFF for these patients [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. It might suggest that for poor responders, the problems associated with oocytes are the major detriments to hamper fertilization.\u003c/p\u003e \u003cp\u003eOne of the most common reasons for TFF is the nucleus-cytoplasmic maturation asynchrony[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Cytoplasmic maturation includes a series of events that are key to oocyte competence, such as the rearrangement of organelles and the accumulation of mRNA, proteins, substrates, and nutrients[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. The calcium store content in the endoplasmic reticulum (ER), which is essential for the fertilization event, also increases markedly during maturation, in company with the rearrangement of ER [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Immature cytoplasm may lead to a failed calcium oscillation following fertilization. In this case, even if a single sperm was injected, no sign of fertilization would be observed. For poor responders, the nucleus-cytoplasmic maturation asynchrony might be more frequent due to the possible alternated follicle growth dynamic, abnormal endocrine response, or other stress and anxiety[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. The function of cumulus cells surrounding the oocyte which promotes cytoplasm/nucleus maturation through an autocrine/paracrine mechanism may also be impaired in the poor responders [\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCompared with conventional IVF, ICSI requires an earlier denudation, leading to a shorter in vitro incubation of the cumulus-oocyte complex. Several studies have shown that the interval between oocyte retrieval and denudation may affect the outcomes of ICSI [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e] and some authors suggested that a longer interval might be associated with a better outcome[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. A longer interval may allow the oocytes to reach full maturity with the somatic cell compartment[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. For oocytes with a potential nucleus-cytoplasmic maturation asynchrony problem, such extended culture before insemination might rescue the immaturity. A possible interpretation for the lower TFF in conventional IVF in our cohort may be that a longer denudation interval may partially reserve the synchronized nucleus-cytoplasmic maturation. On the other hand, however, immature or over-mature cytoplasm might also lead to polyspermy when conventional IVF is used [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eWith conventional IVF, a higher multiple pronuclei (MPN) rate was observed in the cohort. It is generally accepted that MPN formation is due to the abnormal extrusion of the second polar body or to abnormal fertilization with multiple sperm[\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. With the sign of the extrusion of the second polar body, polyspermy is suspected. Polyspermy could be due to the aging of oocytes or a high number of capitated sperm at the fertilization site [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Practically, these two factors may be additive. The routine sperm concentration for insemination may be fine for oocytes with good competence but lead to polyspermy in oocytes with reduced cortical granule function. Reducing the sperm concentration at the fertilization site with methods such as droplet insemination may be a possible alternative to avoid polyspermy [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough there have been several previous studies concerning the use of ICSI in patients with low oocyte yield (1\u0026ndash;2) and non-sever male infertility[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan additionalcitationids=\"CR27 CR28\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], considerable heterogeneity was found when comparing these data (Supplementary Figure\u003cspan refid=\"MOESM4\" class=\"InternalRef\"\u003eS4\u003c/span\u003e). While the majority of the studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] suggested a fertilization rate favored ICSI, the work of Wu et al., and Sfontouris et al. suggested similar fertilization rates between IVF and ICSI in patients with non-sever male infertility [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The source of heterogeneity may be from the patients` characteristics or practices of laboratories. Considering the relatively small sample size of these studies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], the confounders may lead to considerable fluctuation of outcomes. As our data have shown, the differences in TFF became diminished when the age of patients increased (Supplementary Figure \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e, S3). On the other hand, however, since the studies were retrospective, inclusion bias may also be considerable. Imbalances in oocyte maturity rates between IVF and ICSI groups were found in several studies [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The proportion of MII was usually higher in ICSI patients. For instance, Wang et al. showed a significantly higher MII rate in the ICSI group than in the IVF group in patients with one oocyte and also a higher cumulative live birth rate per cycle [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Since ICSI could only be given to mature oocytes following denudation, it is less clear whether cycles with immature or degenerated oocytes were excluded in these studies. Considering the clinical scenarios, the intention-to-treat inclusion rather than per-protocol inclusion may be more meaningful to the decision-making for patients with very low oocyte yield. The heterogeneity calls for higher-quality evidence on this issue. Our data contribute to the issue by giving evidence in indication-matched, intention-to-treat patients.\u003c/p\u003e \u003cp\u003eSimilar to fertilization, the reports concerning the effect of ICSI on pregnancy following an initiated cycle in patients with extremely low responses are heterogeneous [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR25 CR26 CR27 CR28\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Wang et al. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] suggested a cumulative pregnancy rate favoring the ICSI group, which conflicts with our study and Xi et al. [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. While low oocyte yield leads to a very limited chance of transfer, earlier studies only reported pregnancies following fresh transfer [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR26 CR27\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. With the increasing use of FET and ovarian stimulation protocols such as the luteal phase stimulation, more recent studies reported cumulative pregnancy or live birth following a complete cycle. Considering the cumulative chance of pregnancy, the latest evidence in normal responders with non-severy infertility has implied that outcomes following complete cycles would be hampered by the ICSI procedure[\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. A similar effect would be expected in patients with very low oocyte yield, although the small sample size, low number of events, and high uncertainty are also expected in these patients.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStrength and limitations\u003c/h2\u003e \u003cp\u003eIn comparison with previous studies, the strength of the study may include a larger sample size, adjustment for a set of covariates using PS matching, and the reporting of the cumulative outcomes per complete cycle. However, the study is also limited by the retrospective design. In addition, due to the low reproductive potential of poor responders, the current sample size may lack sufficient power to detect the difference in CLBR between the groups while the confidence interval may suggest a trend favoring IVF. Considering that the latest level 1 evidence suggested that ICSI may slightly decrease the CLBR in patients with an adjusted risk ratio of 0.89 [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e], a similar difference would be expected in poor responders with a larger sample size.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur data show that for poor responders with only one or two oocytes retrieved, ICSI cannot avoid TFF. Alternatively, it reduces fertilization and cumulative pregnancy rates. It is suggested that ICSI is not a good choice for extremely poor responders even for securing fertilization. Furthermore, the technical complexity, the cost, the potential damage to oocytes, and possible long-term health issues are also potential concerns of this invasive technique [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e].\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJinghua Chen, Jiali Cai, and Jianzhi Ren contribute to conception and design. Zhengfang Liu, Jinghua Chen, Kaijie Chen, Xiaolian Yang and Liying Zhou contribute to the acquisition of data. Jinghua Chen, Lanlan Liu, Jiali Cai, Yurong Chen and Xiaolian Yang contribute to the analysis and interpretation of data. All authors contributed to drafting the article or revising it critically for important intellectual content. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe thank Xinli Wang for her assistance in the data processing. This work was supported by the National Natural Science Foundation of China [grant number 22176159]; the Xiamen Medical Advantage subspecialty construction project [grant number 2018296] and the Wu Jieping Medical Foundation [grant number 320.6750.2024-6-14].\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePalermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992;340:17\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAdamson GD, de Mouzon J, Chambers GM, Zegers-Hochschild F, Mansour R, Ishihara O, et al. International Committee for Monitoring Assisted Reproductive Technology: world report on assisted reproductive technology, 2011. 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Lancet. 2024;S0140-6736(23)02416-9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1.\u0026nbsp;Basic characteristics before and after PS matching for OPU cycles\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"702\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBefore Matching\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 204px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfter Matching\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e \u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIVF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eICSI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eD*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIVF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eICSI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eD*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(N=2159)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(N=413)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(N=401)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(N=401)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e \u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale age, year\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e35.0[31.0,39.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e36.0[32.0,39.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.1149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e36.0[32.0,40.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e36.0[32.0,39.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.0021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 702px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistory of spontaneous miscarriage\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1790 (82.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e344 (83.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0038\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e333 (83.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e334 (83.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e303 (14.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e58 (14.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e60 (15.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e56 (14.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e45 (2.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e6 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e3 (0.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e6 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0075\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e≧3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e21 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e5 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e5 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e5 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParity\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e≧\u003c/strong\u003e\u003cstrong\u003e1 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e686 (31.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e123 (29.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e121 (30.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e121 (30.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 702px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOPU order\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1347 (62.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e95 (23.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.394\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e88 (21.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e95 (23.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0175\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e521 (24.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e176 (42.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.1848\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e188 (46.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e173 (43.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.0374\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e≧3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e291 (13.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e142 (34.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.209\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e125 (31.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e133 (33.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEndometriosis (%)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e282 (13.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e47 (11.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e51 (12.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e47 (11.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePCOs (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e45 (2.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e13 (3.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e12 (3.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e11 (2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.0025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of infertility, year\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e3.90[2.00,6.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e5.00[2.70,7.50]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.2343\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e4.40[2.00,8.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e4.80[2.60,7.50]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.0423\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale BMI, kg/cm\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e21.8[20.1,23.2]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e22.0[20.0,23.1]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e21.9[20.3,23.2]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e21.9[20.0,23.1]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.0267\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBasal FSH, IU/l\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e8.90 [0.40, 1210]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e9.32 [1.88, 698]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0386\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e9.17 [2.31, 34.9]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e9.32 [1.88, 35.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.0024\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBasal LH, IU/l\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e3.85 [0.01, 30.7]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e3.78 [0.880, 62.6]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e3.80 [0.12, 30.4]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e3.75 [0.88, 62.6]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.0025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntral follicle count\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e5.00[3.00,7.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e5.00[3.00,7.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e5.00[3.00,7.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e5.00[3.00,7.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.0199\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale age, year\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e36.0[32.0,40.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e37.0[33.0,41.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.1337\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e37.0[33.0,41.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e37.0[33.0,41.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.0152\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale BMI, kg/cm\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e23.9[21.8,25.9]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e23.9[21.9,26.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e23.9[21.6,26.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e24.0[21.9,26.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0196\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSperm normal morphology rate (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e6.00[4.00,9.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e4.50[3.00,8.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e5.00[3.50,8.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e4.80[3.00,8.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0205\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal motile sperm number\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003ex10\u003csup\u003e6\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e55.9[28.3,100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e27.6[8.34,63.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.572\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e37.6[20.0,67.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e29.2[8.39,63.2]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.0742\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 702px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOvarian stimulation protocols (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLuteal phase\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e87 (4.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e35 (8.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0444\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e36 (9.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e31 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.0125\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMild stimulation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e128 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e21 (5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e20 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e21 (5.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGnRH antagonist\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1029 (47.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e179 (43.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.043\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e183 (45.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e177 (44.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGnRH agonist\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e725 (33.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e138 (33.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e135 (33.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e133 (33.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOther protocols\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e12 (0.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e3 (0.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e2 (0.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e3 (0.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNatural cycle\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e178 (8.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e37 (9.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0071\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e25 (6.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e36 (9.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0274\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGN starting dose, IU\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e225 [0, 300]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e225 [0, 300]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.076\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e225 [0, 300]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e225 [0, 300]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.088\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 276px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOocyte yield\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0447\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0.0175\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e980 (45.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e169 (40.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e161 (40.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e168 (41.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1179 (54.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e244 (59.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e240 (59.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e233 (58.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExtended culture (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e118 (5.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e32 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e26 (6.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e31 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0125\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData were presented as Median [first quartile, third quartile] and mean (SD) for continuous variables and n (percentage) for categorical variables. *D: Standardized difference. The absolute value of D is less than 0.1, cohorts can be considered to be balanced with respect to the demographics being assessed. OPU, oocyte pick up; PCOs, polycystic ovarian syndrome; BMI, body mass index; FSH, follicle-stimulating hormone; LH, luteinizing hormone; GnRH, gonadotropin; GN, gonadotropin.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Clinical outcomes before and after PS matching for OPU cycles\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"726\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e \u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 201px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBefore Matching\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 213px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfter Matching\u003c/strong\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIVF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eICSI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIVF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eICSI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(N=2159)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(N=413)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(N=401)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(N=401)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCanceled ET cycles (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e744 (34.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e165 (40.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0373\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e142 (35.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e157 (39.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0.307\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCycles got no embryo (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e577 (26.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e117 (28.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e101 (25.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e114 (28.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0.339\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFreeze-all cycle (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e167 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e48 (11.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e41 (10.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e43 (10.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0.908\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTFF cycle (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e187 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e58 (14.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e31 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e56 (14.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0.00643\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMature oocyte number\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e1.42 (0.582)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.45 (0.575)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.258\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.47 (0.592)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1.44 (0.577)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0.375\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eMedian [Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e1.00 [0, 2.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.00 [0, 2.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2.00 [0, 2.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1.00 [0, 2.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFertilization rate, (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e85.7 (30.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e76.0 (36.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e86.8 (29.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e76.1 (36.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eMedian [Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e100 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e100 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e100 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e100 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMPN rate, (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e20.80 (42.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e5.33 (22.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e20.00 (42.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e5.24 (22.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eMedian [Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 [0, 100.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0 [0, 100.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0 [0, 100.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e0 [0, 100.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNormal fertilization rate, (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e64.2 (41.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e67.7 (40.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e65.7 (40.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e67.6 (40.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0.426\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eMedian [Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e100 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e100 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e100 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e100 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 255px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCleavage 2PN embryo rate, (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e73.9 (43.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e77.1 (41.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.158\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e76.2 (42.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e76.9 (42.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0.769\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eMedian [Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e100 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e100 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e100 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e100 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAvailable embryo number\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.722 (0.737)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.826 (0.766)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.800 (0.768)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e0.813 (0.760)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0.787\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eMedian [Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e1.00 [0, 2.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.00 [0, 2.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.00 [0, 2.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1.00 [0, 2.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh-quality embryo rate,\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e37.2 (46.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e38.4 (45.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.537\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e40.4 (46.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e38.4 (46.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0.575\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eMedian [Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e0 [0, 100]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCumulative pregnancy, (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e563 (26.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e90 (21.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0765\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e115 (28.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e87 (21.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0.0281\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCLB rate, (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e444 (20.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e72 (17.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.165\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e85 (21.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e69 (17.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0.179\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData were presented as mean (SD) and median [Min, Max] for continuous variables and n (percentage) for categorical variables. TFF, total fertilization failure; PN, pronuclei; MPN, multi pronuclei; CLB, cumulative live birth.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTable 3. Association between insemination protocols and outcomes in patients with one or two oocyte\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"549\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBefore Matching\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfter Matching\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 549px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal fertilization failure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eIVF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eICSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e1.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e1.12, 2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e1.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e1.12, 2.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 549px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCumulative pregnancy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eIVF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eICSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.58, 1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.46, 0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 549px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCumulative live birth\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eIVF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eICSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.60, 1.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.55, 1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.094\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 549px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e OR = Odds Ratio, CI = Confidence Interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eModels were adjusted for female age, female BMI, female basal FSH, LH, AFC, previous maternal history, PCOS, endometriosis, OPU order, male BMI, male age, sperm normal morphology rate, total motile sperm number, stimulation protocol, oocyte yield and extended culture .\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"IVF, ICSI, Normal fertilization rate, Total fertilization failure rate, Cumulative live birth rate, Poor responder","lastPublishedDoi":"10.21203/rs.3.rs-5335385/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5335385/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: To compare the clinical outcomes of extremely poor responders with one or two oocytes who receive in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A retrospective study was carried out in 2572 patients with one or two oocytes retrieved from 2013 to 2022, of which 2159 patients were scheduled to receive IVF treatment and 413 patients were scheduled to receive ICSI treatment. The laboratory parameters and clinical outcomes were compared with adjusted multivariate regression and propensity score (PS) matching.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: In both matched and non-matched cohorts, the total fertilization failure (TFF) rate of the ICSI group was significantly higher than that of the IVF group (P \u0026lt; 0.05), but the multiple fertilization rate of the IVF group was significantly higher than the ICSI group (P \u0026lt; 0.05). After matching, the cumulative pregnancy rate per initiated cycle in the IVF group was significantly higher than in the ICSI group (28.7% vs 21.7, P=0.028). However, the difference in cumulative live births did not reach significant (21.2 % vs 17.2 %, P =0.179). The adjusted odds ratios for TFF, cumulative pregnancy, and cumulative live birth comparing ICSI versus IVF in multivariate models were 1.65(95%CI: 1.12, 2.43), 0.65(95%CI: 0.46, 0.91), and 0.76(95%CI:0.55, 1.04) respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: In poor responders with one or two oocytes retrieved, ICSI insemination cannot avoid TFF, and it may hamper the cumulative pregnancy rate.\u003c/p\u003e","manuscriptTitle":"Intracytoplasmic sperm injection hampers fertilization rate and pregnancy per initiated cycle in patients with extremely poor ovarian response","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-06 09:48:08","doi":"10.21203/rs.3.rs-5335385/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-02-17T14:06:17+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-02-17T13:38:36+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-02-04T19:55:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"39473941152107297478571134798084373957","date":"2025-01-15T14:07:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"147358343131272766387929382154748752344","date":"2025-01-13T11:29:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-12-11T17:17:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-27T12:15:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-26T07:39:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Gynecology and Obstetrics","date":"2024-10-26T03:45:12+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f8aa8c53-5f18-4123-ae8c-aaeacefa884a","owner":[],"postedDate":"November 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-05T16:03:21+00:00","versionOfRecord":{"articleIdentity":"rs-5335385","link":"https://doi.org/10.1007/s00404-025-08033-3","journal":{"identity":"archives-of-gynecology-and-obstetrics","isVorOnly":false,"title":"Archives of Gynecology and Obstetrics"},"publishedOn":"2025-04-30 15:57:32","publishedOnDateReadable":"April 30th, 2025"},"versionCreatedAt":"2024-11-06 09:48:08","video":"","vorDoi":"10.1007/s00404-025-08033-3","vorDoiUrl":"https://doi.org/10.1007/s00404-025-08033-3","workflowStages":[]},"version":"v1","identity":"rs-5335385","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5335385","identity":"rs-5335385","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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