Reproductive outcomes in women with advanced endometriosis in fresh versus frozen embryo transfer cycles.

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Ahmed Shoukry, Wael Samir El Gazeirly, Mohamed Abdelkader Khattab, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4335275/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Aug, 2024 Read the published version in Middle East Fertility Society Journal → Version 1 posted 5 You are reading this latest preprint version Abstract Background: ART in women with endometriosis is associated with poor quality of the retrieved oocytes and lower fertilization and pregnancy rates, reflecting that endometriosis may influence fertility by altering the quality of both the oocyte and embryo quality and also by impairing the endometrial receptivity. On comparing endometriosis affected patients to healthy counterparts, many differences were demonstrated at the endometrial level. Thus, choosing the appropriate method of embryo transfer is of utmost importance, particularly for patients with advanced endometriosis. Objective: The aim of the present study was to compare the reproductive outcomes between fresh and frozen embryo transfer cycles in women with advanced endometriosis. A retrospective cohort study was conducted for patients recruited from two IVF centers, Alexandria, Egypt. Careful review of paper and electronic medical records of infertile women (primary, relative, or secondary infertility) aged 18 – 37 years who were diagnosed with advanced endometriosis by means of laparoscopy and were scheduled for ICSI followed by either fresh embryo transfer (group I) or freeze all embryos and deferred embryo transfer (group II) of day 5 embryo(s) were included in the study. Results : Two hundred and eleven women were eligible and included in the study. Women in each study group were matched regarding baseline characteristics. Clinical pregnancy, implantation, ongoing pregnancy rates were statistically significant higher in the group of frozen embryo transfer (p<0.001). Miscarriage rate was found to be higher in the group of fresh transfer compared to FET group but without a statistical significance (20.9% vs 9.2%, p = 0.072). Conclusion: In women with advanced endometriosis, freeze all policy is associated with better implantation, ongoing pregnancy rates and it is recommended to be adopted when appropriate in such patients. endometriosis freeze all frozen embryo transfer ongoing pregnancy rate Figures Figure 1 Introduction Endometriosis is defined as a disease characterized by the presence of endometrium resembling epithelium and/or stroma outside the endometrium and myometrium, usually in association with an inflammatory process ( 1 ) It roughly affects 10% (approximately 190 million women worldwide) of girls and women of reproductive age globally Endometriosis - infertility relationship has been a point of debate for decades. The fecundity ranges from 15–20% per month in normal couples, and declines with age. Patients with endometriosis have a decreased monthly fecundity of about 0.2% – 1% each month.( 2 , 3 ) Moreover, endometriosis is associated with decline in the live birth rate (LBR) ( 4 ). Although ART remain the most effective treatment modality for infertile women with endometriosis, it still yields poor outcomes as ART could not overcome all the substantial effects of endometriosis ( 5 , 6 ). Endometriosis affected women have declined pregnancy and implantation rates in comparison to women without endometriosis ( 7 ). It was noticed that endometriosis has undesirable effect on the pregnancy, miscarriage, and live birth rates. It was found that ART outcomes, as the quality of the retrieved oocytes and fertilization rate, are negatively influenced by the existence of endometriosis, reflecting that endometriosis influence fertility by altering the quality of both the oocyte and embryo quality and by impairing the endometrial receptivity ( 6 ). On comparing endometriosis affected patients to healthy counterparts, many differences were demonstrated at the endometrial level ( 8 ), which define the decline in the receptivity of the endometrium. Thus, choosing the appropriate method of embryo transfer is of utmost importance, particularly for patients with advanced endometriosis. In the view of the impact of the supraphysiological level of hormones associated with stimulation in fresh embryo transfer on the uterine environment during early peri-implantation, it was demonstrated that flowing of blood in the endometrium and sub-endometrium is reduced in stimulated cycles in comparison to natural cycles as evaluated by three-dimensional power Doppler ultrasonography.( 9 ) Furthermore, histopathologic alterations of the stimulated endometrium were reported, this includes advancement in the maturation of the endometrium,( 10 ) and premature development of channel systems in the nucleolus.( 11 ) On the other hand, in frozen embryo transfer (FET) cycles, endometrial growth can be more controlled than in fresh cycles ( 12 ). Based on that, the use of frozen embryos, avoided the supraphysiological hormone level found during ovarian hyper stimulation in In vitro Fertilization (IVF)/ ICSI with fresh embryo transfer, that leads to an unfavorable environment for implantation and have been found to have detrimental effects on the endometrial receptivity, irrespective of the amount of retrieved oocytes or levels of progesterone (P) ( 13 – 16 ). Therefore, the aim of the present study was to compare the reproductive outcomes between fresh and frozen embryo transfer cycles in women with advanced endometriosis. Study design & setting: A retrospective cohort study was conducted for patients recruited from two IVF centers (Agial Fertility center & Dar-Elkhosoba center), Alexandria, Egypt. Materials & Methods Careful review of paper and electronic medical records of infertile women (primary, relative, or secondary infertility) aged 18–37 years who were diagnosed with advanced endometriosis, stage III/IV r-ASRM classification ( 17 ), by means of laparoscopy and were scheduled for intracytoplasmic sperm injection (ICSI) followed by either fresh embryo transfer or freeze all embryos and deferred embryo transfer of day 5 embryo(s) in the period from January 2018 till December 2021 were included in the study. Couples with abnormal semen analysis of the male partner, recurrent implantation failure in previous ICSI trials, and women with uterine lesions such as fibroids, adenomyosis, polypi, uterine septum, and women with no available follow up data were excluded from the study. The study protocol was approved from the Ethics committee of Faculty of Medicine, Alexandria University. Ovarian stimulation all the women enrolled in the study underwent controlled ovarian stimulation via the fixed GnRH antagonist protocol. Before ovarian stimulation, women were pretreated with combined oral contraceptive pills for 2–3 weeks. On day 2 of the menstrual cycle (stimulation day 1), patients received a fixed daily dose of recombinant FSH or combination of rec-FSH and human menopausal gonadotropins. Starting on day 5 of stimulation, patients underwent monitoring with transvaginal ultrasound and serial assessment of oestradiol every 2–3 days as required. A daily subcutaneous dose of 0.25 mg of GnRH antagonist cetrorelix was initiated on day 6 of ovarian stimulation and continued up to the day of trigger administration. When at least three follicles reached 17 mm in diameter final oocyte maturation was triggered using 10,000 IU of human chorionic gonadotropin (hCG). Ovum pickup (OPU) was performed 35–36 hours of hCG administration. Mature oocytes were inseminated by means of intracytoplasmic sperm injection and cultured to blastocyst stage. Group (I): women who underwent fresh embryo transfer (ET) : combined vaginal suppositories and intramuscular progesterone in oil injections were started on day of OPU, and ET was performed 5 days after P administration. Group (II): women who underwent frozen embryo transfer after endometrial preparation through artificial or programmed cycle : after vitrification of the available embryos, in the subsequent cycle women underwent ovarian suppression by combined pills for 2–3 weeks then endometrial preparation was achieved with a daily dose of 8 mg of estradiol valerate for at least 12–14 days. When endometrium thickness was at least 8 mm and E2 level reached at least 200 pg/dl, progesterone as vaginal suppositories and intramuscular in oil injection were administrated and ET of thawed embryos was performed after 5 days of P therapy. Outcome variables the primary outcome of the study was the ongoing pregnancy rate (OPR) defined as pregnancy progressed beyond 14 weeks’ gestation. Secondary outcomes include; implantation rate, defined as the number of intrauterine gestational sacs observed by trans-vaginal ultrasound divided by the number of transferred embryos, clinical pregnancy rate (CPR), calculated by considering clinical pregnancy, determined by the visualization of a viable gestational sac within the uterine cavity by ultrasound 3– 4 weeks after embryo transfer, and miscarriage rate, defined as the number of cases who aborted (after a confirmed clinical pregnancy) divided by the total number of pregnant cases. Statistical analysis Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp) Qualitative data were described using number and percent. The Kolmogorov-Smirnov test was used to verify the normality of distribution Quantitative data were described using range (minimum and maximum), mean, standard deviation, median and interquartile range (IQR). Significance of the obtained results was judged at the 5% level. The used tests were Chi-square test for categorical variables, to compare between different groups, Student t-test for normally distributed quantitative variables, to compare between two studied groups, and Mann Whitney test for abnormally distributed quantitative variables, to compare between two studied groups. Results Over the 4-year study period, there were 237 women with advanced endometriosis underwent either fresh or frozen embryo transfer cycles, out of them 211 women were eligible and included in the study, figure (1) demonstrates the flow chart of the study. The study included 211 patients divided into two groups as follows, Group (I) includes 103 patients who underwent fresh embryo transfer. Group (II) includes 108 patients who underwent frozen embryo transfer. Figure (1): Study flowchart Regarding the baseline characteristics of both groups (table 1), patients in the two study groups were matched regarding mean age, infertility duration, type of infertility (primary or secondary), body mass index, and AMH level. Table (1): Comparison between the two studied groups according to the baseline characteristics : Baseline Characteristics Fresh ET (n = 103) Frozen ET (n = 108) Test of sig. P Mean age (years) 31.22 ± 4.94 30.87 ± 4.45 t = 0.546 0.586 Median infertility duration(IQR) years 4.0 (3.0–7.0) 4.25 (3.0–8.0) U = 5266.50 0.502 Mean BMI (kg/m2) 25.83 ± 3.26 25.01 ± 3.04 t = 1.903 0.058 Infertility type No. % No. % χ 2 = 3.987 0.136 Primary 76 73.8 71 65.7 Secondary 17 16.5 16 14.8 Relative 10 9.7 21 19.4 Mean AMH 1.91 ± 1.11 2.21 ± 1.31 t = 1.813 0.071 As shown in table (2), the number of embryos transferred was either a single embryo or two embryos, and there was no statistical significant difference between the two groups (p 0.473), for the quality of the embryos transferred that were either high quality embryos alone or low quality embryos alone or both of them together, both groups showed no statistically significant difference (p 0.325). Table (2): Comparison between the two studied groups according to the embryos transferred : Embryos Transferred Fresh ET (n = 103) Frozen ET (n = 108) χ 2 P No. % No. % Number Single embryo 47 45.6 44 40.7 0.514 0.473 Two embryos 56 54.4 64 59.3 Quality Low 26 25.2 22 20.4 2.246 0.325 High 73 70.9 77 71.3 High + Low 4 3.9 9 8.3 The clinical pregnancy rate was significantly higher in the frozen embryo transfer group than the fresh group (82 patients (75.9%) vs 46 patients (44.7%) (p < 0.001)), again the FET group showed a significantly higher implantation rate in comparison to the fresh group as illustrated in table (3). (30.8% vs 54.1% (p < 0.001)). Table (3): Comparison between the two studied groups according clinical pregnancy and implantation rates. Fresh ET (n = 103) Frozen ET (n = 108) χ 2 p No. % No. % Clinical pregnancy rate 46 44.7 82 75.9 21.597 * < 0.001 * Number of GS seen by TVU (after 3–5 weeks) 49 93 <0.001 * Number of transferred embryos 159 172 Implantation rate 30.8% 54.1% Out of the 128 pregnant females in the study, 3 pregnant patients dropped out from the fresh group, and 6 pregnant patients dropped out from the frozen group, those 9 patients were excluded from our statistical results while estimating the miscarriage rate. The miscarriage rate was higher in the fresh ET group than in the frozen ET group, however, the difference did not reach statistical significance (9 (20.9%) vs 7 (9.2%) (p = 0.072). As for the primary outcome of the study, the ongoing pregnancy rate, out of the 211 patients included in our study, there was no available data for 9 pregnant patients, 3 patients in group 1 and 6 patients in group 2, those 9 patients were excluded from our statistical analysis while estimating the ongoing pregnancy rate. Sixty-nine patients in the frozen embryo transfer group (69/102 = 67.6%) continued their pregnancy beyond 14 weeks, while 33 patients (34/100 = 34%) of the fresh embryo transfer group continued their pregnancy beyond 14 weeks, showing a significant statistical higher ongoing pregnancy rates in the frozen embryo transfer group (p < 0.001). Table (4) Table (4): Comparison between the two studied groups according to the ongoing pregnancy. Fresh ET Frozen ET χ 2 p No. (%) No. (%) Ongoing pregnancy (n = 100 # ) (n = 102 # ) 22.876 * < 0.001 * 34 (34.0%) 69 (67.6%) Discussion The present study showed that OPR in women with advanced endometriosis is significantly higher in the group of frozen embryo transfer compared to the fresh embryo transfer group (67.6% vs. 34% respectively). Regarding the secondary outcomes, there was a statistically significant higher implantation and clinical pregnancy rates also in the frozen embryo transfer group. To best of our knowledge, only few studies have addressed the issue of freeze all policy in women with advanced endometriosis. In agreement with the findings of the current study, Wu et al.,( 18 ) conducted a retrospective study that encompassed 1651 women with advanced stages of endometriosis performing ICSI. After matching, 506 women and 255 women were eligible in the freeze-all group in fresh group, respectively. In their matched cohort study, the implantation, CPR and LBR were significantly higher in the FET group in comparison to the fresh groups. Those results coincide with the current study in all perspectives except for the LBR as it was not included in the outcomes for the study. However, the present study differs from Wu et al., where in their study, the development of the embryo was accessed on day 3, and the embryos selected to be transferred were high-quality cleavage-stage embryos only (at least six blastomeres with ≤ 20% fragmentation based on the Cummins' Criteria). In the fresh embryo transfer group, patients were arranged for a day 3 fresh embryo transfer, and vitrification of the extra embryos. For the FET, vitrification on day 3 of the entire cohort of good quality embryos. While in the present study, embryo development was assessed on day 5 and patients performing fresh transfer were scheduled for a day-5 ET, while in the frozen group, the embryos were vitrified on day 5, and embryo transfer was not exclusively for high quality embryos, but in some cases average or low quality embryos were transferred either alone or in combination with a high quality embryo. Again the results of the present study coincided with a matched cohort prospective study conducted by Bourdon et al. ( 19 ),they compared the results of FET to fresh ET in women having endometriosis, where the FET group involved 135 women and the fresh group involved 424 matched women. CPR was of higher significance toward the FET group in comparison to the fresh group, also the ongoing pregnancy rate showed greater statistical significance in the FET group (34.8%) in comparison to the fresh-ET group (17.8%) (p = 0.005), and the live birth rate as well was of higher significance in FET in comparison to fresh embryo transfer group. Another interesting study conducted by Mohamed et al. ( 20 ), a retrospective, database-searched cohort study. The study included two groups, the first group had freshly transferred embryos while the second group performed frozen embryo transfer. The primary outcome for the study was the live birth rate, while the secondary outcomes included the clinical pregnancy rate and the miscarriage rate. Out of the total number of cases, 415 (5.7%) had infertility attributed to endometriosis, in whom frozen ET cycles were associated with a relatively similar clinical pregnancy rate and live birth rate, in comparison to the clinical pregnancy rate and live birth rate of fresh ET cycles, showing no significant difference. Nevertheless, the study of Mohamed et al. differs from the present study as they considered other causes of infertility rather than endometriosis alone as a sole factor of infertility, it also concluded that there was no significant difference between FET over the fresh ET in cases of endometriosis concerning CPR (18.2 vs. 20.2% respectively) and LBR (16.9% vs. 15.5% respectively). In accordance, a recent systematic review and meta-analysis conducted by Chang et al. ( 21 ), aimed at evaluating if FET has the ability to reimpose optimal receptivity targeting better ART results in patients with endometriosis. A total of six studies with moderate methodological quality were included in the meta-analysis. Three thousands and ten patients with endometriosis who underwent ICSI were included in the studies; 1777 performed FET, and 1233 performed fresh ET. LBR was significantly higher in the FET group in comparison to the fresh group. Although that CPR was similar between the two study groups, there was a significantly higher miscarriage rate in the fresh group. The endometrium of endometriosis-affected women is different from that of healthy, unaffected women ( 8 ), which could be the main reason for the decline in endometrial receptivity quality. Thus, it is crucial to select the right embryo transfer technique, particularly for women who have severe endometriosis. The effects of ovarian stimulation in fresh ET cycles on the early peri-implantation uterine milieu have been documented in a number of studies, three-dimensional power Doppler ultrasonography measurements have revealed that stimulated cycles have reduced endometrial and subendometrial blood flow in comparison to normal cycles ( 9 ). Furthermore, certain pathologic alterations of the stimulated endometrium have been verified, such as the progression of endometrial maturation ( 10 ), as well as the early establishment of nucleolar channel systems ( 11 ). Additionally, a number of researchers have demonstrated that during fresh embryo transfer cycles, there are abnormalities in the transcriptional activity of genes related to endometrial receptivity ( 22 – 24 ). The alterations indicated above are linked to the hyperestrogenic environment created during fresh IVF, which might subsequently hinder early embryonic adhesion ( 18 , 25 ), and consequently, the embryos' capacity to implant. It follows that the current study's findings regarding implantation, clinical pregnancy, and ongoing pregnancy are better in FET cycles. Our study has the advantage of being one of the few studies that addressed the role FET in endometriosis affected women and was conducted for a fair number of patients, moreover, this study focused on advanced endometriosis being the sole factor of infertility in the studied patients, excluding any other infertility related factors, however the main study limitation was being a retrospective analysis depending on the availability of complete medical records and the follow up stopped at 14 weeks of gestation. Conclusions The present study provides affirmation that the frozen embryo transfer in cases of advanced endometriosis yields better fertility outcomes in comparison to fresh embryo transfer in terms of clinical and ongoing pregnancy rates. Abbreviations ART assisted reproductive technologies LBR live birth rate FET frozen embryo transfer ASRM American Society of Reproductive Medicine CPR clinical pregnancy rate OPR ongoing pregnancy rate IVF in vitro fertilization ICSI intracytoplasmic sperm injection GnRH gonadotropin releasing hormone AMH anti-mullerian hormone Declarations Ethical approval and consent to participate The study protocol was approved by the ethical committee of the Faculty of Medicine, Alexandria University, Egypt. No informed consent was required due to the retrospective design of the study. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Author information & affiliations Hesham Adel & Wael El El Gazeirly are Assistant Professor of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Faculty of Medicine, Alexandria University, Egypt. Ahmed Shoukry is a Lecturer of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Faculty of Medicine, Alexandria University, Egypt Mohamed Khattab is Senior Registrar of Obstetrics and Gynecology, Alexandria University Hospitals, Egypt. Contribution Hesham Adel & Ahmed Shoukry were the main authors responsible of the research and writing the paper. Mohamed Khattab was responsible for the data collection, Wael El Gazeirly was responsible for reviewing and revising the paper. All authors read and approved the final manuscript. Consent for publication Not applicable. Acknowledgments Not applicable. Competing interests The authors declare that they have no competing interests. Funding The authors received no external funds. References Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, De Mouzon J, Sokol R, Cooke ID (2017) The international glossary on infertility and fertility care, 2017. 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J Clin Endocrinol Metab 89(11):5742–5752 Horcajadas JA, Riesewijk A, Polman J, van Os R, Pellicer A, Mosselman S, Simón C (2004) Effect of controlled ovarian hyperstimulation in IVF on endometrial gene expression profiles. Mol Hum Reprod 11(3):195–205 Haouzi D, Assou S, Mahmoud K, Tondeur S, Rème T, Hedon B, Hamamah S (2009) Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients. HumReprod 24(6):1436–1445 Valbuena D, Martin J, de Pablo JL, Remohı́ J, Pellicer A, Simón C (2001) Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo. Fertil Steril 76(5):962–968 Cite Share Download PDF Status: Published Journal Publication published 08 Aug, 2024 Read the published version in Middle East Fertility Society Journal → Version 1 posted Reviewers agreed at journal 15 May, 2024 Reviewers invited by journal 14 May, 2024 Editor invited by journal 11 May, 2024 Editor assigned by journal 29 Apr, 2024 First submitted to journal 27 Apr, 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4335275","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":302520817,"identity":"99a45843-9a13-4b2f-8f76-545cebe5456b","order_by":0,"name":"Ahmed Shoukry","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABH0lEQVRIie2RMUvEMBTHX6nkluqtKWLFb9ASqA79MO2SyQ4ucmNAyA0Krgdy36FSqOtBsC6prhFuqMtNN3QU7GCKCAo92lEwP0hIwvvxf48AGAx/EayXA6tuA4hnkTftXmsAf5xSS0pcBhaLxyrWGxdJthpQpnfXSb1t154vqw1OOE3yp5vTWndIYCIes76QdZUHS74hfjUPcfwckULKgMWShuBQqvpiVFoc7jPdzwtCOL6kR4U6D1jCRQTYCfuUY5U+fDjtt4KElS8GFF+n2A7SSsW1wsVJhr+UcJcSqDR3l1wQV5b2mR6BYFleLLoD2jGLp9L7ZtsK70BS6/W9+8r5VdY0syi4nYiyd/wf7OFfVzRQ3mE3I4oMBoPhH/IJV0B0L5zuXH8AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-3422-3822","institution":"Faculty of Medicine of Alexandria University: Alexandria University Faculty of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Ahmed","middleName":"","lastName":"Shoukry","suffix":""},{"id":302520818,"identity":"d2b6af87-024e-407d-b708-4e3934746ff7","order_by":1,"name":"Wael Samir El Gazeirly","email":"","orcid":"","institution":"Alexandria Medicine: Alexandria University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Wael","middleName":"Samir El","lastName":"Gazeirly","suffix":""},{"id":302520819,"identity":"15c44d58-b3f2-445d-ad5f-02a77075c900","order_by":2,"name":"Mohamed Abdelkader Khattab","email":"","orcid":"","institution":"Alexandria Medicine: Alexandria University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"Abdelkader","lastName":"Khattab","suffix":""},{"id":302520820,"identity":"d706531c-689a-4a6a-80cb-55c1f7d11a5d","order_by":3,"name":"Hesham Mahmoud Adel Abdelmoneim","email":"","orcid":"","institution":"Faculty of Medicine of Alexandria University: Alexandria University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hesham","middleName":"Mahmoud Adel","lastName":"Abdelmoneim","suffix":""}],"badges":[],"createdAt":"2024-04-27 19:19:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4335275/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4335275/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s43043-024-00200-x","type":"published","date":"2024-08-08T15:58:10+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":57442041,"identity":"66f4e5e9-7f59-40f4-b94b-3af708387365","added_by":"auto","created_at":"2024-05-30 18:43:58","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":125239,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy flowchart\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4335275/v1/837a4f2b22decba751969c51.jpeg"},{"id":62298484,"identity":"9d09a932-bba5-4f39-966a-c64e6066a43f","added_by":"auto","created_at":"2024-08-12 16:13:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":774908,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4335275/v1/e1dd889b-749d-4191-bb16-e4c0102b4241.pdf"}],"financialInterests":"","formattedTitle":"Reproductive outcomes in women with advanced endometriosis in fresh versus frozen embryo transfer cycles.","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEndometriosis is defined as a disease characterized by the presence of endometrium resembling epithelium and/or stroma outside the endometrium and myometrium, usually in association with an inflammatory process (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) It roughly affects 10% (approximately 190\u0026nbsp;million women worldwide) of girls and women of reproductive age globally\u003c/p\u003e \u003cp\u003eEndometriosis - infertility relationship has been a point of debate for decades. The fecundity ranges from 15\u0026ndash;20% per month in normal couples, and declines with age. Patients with endometriosis have a decreased monthly fecundity of about 0.2% \u0026ndash; 1% each month.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Moreover, endometriosis is associated with decline in the live birth rate (LBR) (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Although ART remain the most effective treatment modality for infertile women with endometriosis, it still yields poor outcomes as ART could not overcome all the substantial effects of endometriosis (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Endometriosis affected women have declined pregnancy and implantation rates in comparison to women without endometriosis (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIt was noticed that endometriosis has undesirable effect on the pregnancy, miscarriage, and live birth rates. It was found that ART outcomes, as the quality of the retrieved oocytes and fertilization rate, are negatively influenced by the existence of endometriosis, reflecting that endometriosis influence fertility by altering the quality of both the oocyte and embryo quality and by impairing the endometrial receptivity (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). On comparing endometriosis affected patients to healthy counterparts, many differences were demonstrated at the endometrial level (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), which define the decline in the receptivity of the endometrium. Thus, choosing the appropriate method of embryo transfer is of utmost importance, particularly for patients with advanced endometriosis.\u003c/p\u003e \u003cp\u003eIn the view of the impact of the supraphysiological level of hormones associated with stimulation in fresh embryo transfer on the uterine environment during early peri-implantation, it was demonstrated that flowing of blood in the endometrium and sub-endometrium is reduced in stimulated cycles in comparison to natural cycles as evaluated by three-dimensional power Doppler ultrasonography.(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) Furthermore, histopathologic alterations of the stimulated endometrium were reported, this includes advancement in the maturation of the endometrium,(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) and premature development of channel systems in the nucleolus.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOn the other hand, in frozen embryo transfer (FET) cycles, endometrial growth can be more controlled than in fresh cycles (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Based on that, the use of frozen embryos, avoided the supraphysiological hormone level found during ovarian hyper stimulation in In vitro Fertilization (IVF)/ ICSI with fresh embryo transfer, that leads to an unfavorable environment for implantation and have been found to have detrimental effects on the endometrial receptivity, irrespective of the amount of retrieved oocytes or levels of progesterone (P) (\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTherefore, the aim of the present study was to compare the reproductive outcomes between fresh and frozen embryo transfer cycles in women with advanced endometriosis.\u003c/p\u003e\n\u003ch3\u003eStudy design \u0026 setting:\u003c/h3\u003e\n\u003cp\u003eA retrospective cohort study was conducted for patients recruited from two IVF centers (Agial Fertility center \u0026amp; Dar-Elkhosoba center), Alexandria, Egypt.\u003c/p\u003e"},{"header":"Materials \u0026 Methods","content":"\u003cp\u003eCareful review of paper and electronic medical records of infertile women (primary, relative, or secondary infertility) aged 18\u0026ndash;37 years who were diagnosed with advanced endometriosis, stage III/IV r-ASRM classification (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), by means of laparoscopy and were scheduled for intracytoplasmic sperm injection (ICSI) followed by either fresh embryo transfer or freeze all embryos and deferred embryo transfer of day 5 embryo(s) in the period from January 2018 till December 2021 were included in the study.\u003c/p\u003e \u003cp\u003eCouples with abnormal semen analysis of the male partner, recurrent implantation failure in previous ICSI trials, and women with uterine lesions such as fibroids, adenomyosis, polypi, uterine septum, and women with no available follow up data were excluded from the study. The study protocol was approved from the Ethics committee of Faculty of Medicine, Alexandria University.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eOvarian stimulation\u003c/strong\u003e \u003cp\u003eall the women enrolled in the study underwent controlled ovarian stimulation via the fixed GnRH antagonist protocol. Before ovarian stimulation, women were pretreated with combined oral contraceptive pills for 2\u0026ndash;3 weeks. On day 2 of the menstrual cycle (stimulation day 1), patients received a fixed daily dose of recombinant FSH or combination of rec-FSH and human menopausal gonadotropins. Starting on day 5 of stimulation, patients underwent monitoring with transvaginal ultrasound and serial assessment of oestradiol every 2\u0026ndash;3 days as required. A daily subcutaneous dose of 0.25 mg of GnRH antagonist cetrorelix was initiated on day 6 of ovarian stimulation and continued up to the day of trigger administration. When at least three follicles reached 17 mm in diameter final oocyte maturation was triggered using 10,000 IU of human chorionic gonadotropin (hCG). Ovum pickup (OPU) was performed 35\u0026ndash;36 hours of hCG administration. Mature oocytes were inseminated by means of intracytoplasmic sperm injection and cultured to blastocyst stage.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003e \u003cb\u003eGroup (I): women who underwent fresh embryo transfer (ET)\u003c/b\u003e: combined vaginal suppositories and intramuscular progesterone in oil injections were started on day of OPU, and ET was performed 5 days after P administration.\u003c/p\u003e \u003cp\u003e \u003cb\u003eGroup (II): women who underwent frozen embryo transfer after endometrial preparation through artificial or programmed cycle\u003c/b\u003e: after vitrification of the available embryos, in the subsequent cycle women underwent ovarian suppression by combined pills for 2\u0026ndash;3 weeks then endometrial preparation was achieved with a daily dose of 8 mg of estradiol valerate for at least 12\u0026ndash;14 days. When endometrium thickness was at least 8 mm and E2 level reached at least 200 pg/dl, progesterone as vaginal suppositories and intramuscular in oil injection were administrated and ET of thawed embryos was performed after 5 days of P therapy.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eOutcome variables\u003c/strong\u003e \u003cp\u003ethe primary outcome of the study was the ongoing pregnancy rate (OPR) defined as pregnancy progressed beyond 14 weeks\u0026rsquo; gestation. Secondary outcomes include; implantation rate, defined as the number of intrauterine gestational sacs observed by trans-vaginal ultrasound divided by the number of transferred embryos, clinical pregnancy rate (CPR), calculated by considering clinical pregnancy, determined by the visualization of a viable gestational sac within the uterine cavity by ultrasound 3\u0026ndash; 4 weeks after embryo transfer, and miscarriage rate, defined as the number of cases who aborted (after a confirmed clinical pregnancy) divided by the total number of pregnant cases.\u003c/p\u003e \u003c/p\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData were fed to the computer and analyzed using IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp) Qualitative data were described using number and percent. The Kolmogorov-Smirnov test was used to verify the normality of distribution Quantitative data were described using range (minimum and maximum), mean, standard deviation, median and interquartile range (IQR). Significance of the obtained results was judged at the 5% level. The used tests were Chi-square test for categorical variables, to compare between different groups, Student t-test for normally distributed quantitative variables, to compare between two studied groups, and Mann Whitney test for abnormally distributed quantitative variables, to compare between two studied groups.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOver the 4-year study period, there were 237 women with advanced endometriosis underwent either fresh or frozen embryo transfer cycles, out of them 211 women were eligible and included in the study, figure (1) demonstrates the flow chart of the study. The study included 211 patients divided into two groups as follows, Group (I) includes 103 patients who underwent fresh embryo transfer. Group (II) includes 108 patients who underwent frozen embryo transfer.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure (1): Study flowchart\u003c/b\u003e \u003c/p\u003e \u003cp\u003eRegarding the baseline characteristics of both groups (table 1), patients in the two study groups were matched regarding mean age, infertility duration, type of infertility (primary or secondary), body mass index, and AMH level.\u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;(1): Comparison between the two studied groups according to the baseline characteristics\u003c/b\u003e:\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline Characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eFresh ET \u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;103)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eFrozen ET \u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;108)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTest of sig.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMean age (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e31.22\u0026thinsp;\u0026plusmn;\u0026thinsp;4.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e30.87\u0026thinsp;\u0026plusmn;\u0026thinsp;4.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003et\u0026thinsp;=\u0026thinsp;\u003c/p\u003e \u003cp\u003e0.546\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.586\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian infertility duration(IQR) years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e4.0 (3.0\u0026ndash;7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e4.25 (3.0\u0026ndash;8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eU\u0026thinsp;=\u0026thinsp;\u003c/p\u003e \u003cp\u003e5266.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.502\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMean BMI (kg/m2)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e25.83\u0026thinsp;\u0026plusmn;\u0026thinsp;3.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e25.01\u0026thinsp;\u0026plusmn;\u0026thinsp;3.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003et\u0026thinsp;=\u0026thinsp;\u003c/p\u003e \u003cp\u003e1.903\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInfertility type\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e=\u003c/p\u003e \u003cp\u003e3.987\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.136\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRelative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMean AMH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2.21\u0026thinsp;\u0026plusmn;\u0026thinsp;1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003et\u0026thinsp;=\u0026thinsp;1.813\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.071\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAs shown in table (2), the number of embryos transferred was either a single embryo or two embryos, and there was no statistical significant difference between the two groups (p 0.473), for the quality of the embryos transferred that were either high quality embryos alone or low quality embryos alone or both of them together, both groups showed no statistically significant difference (p 0.325).\u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;(2): Comparison between the two studied groups according to the embryos transferred\u003c/b\u003e:\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eEmbryos Transferred\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eFresh ET \u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;103)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eFrozen ET \u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;108)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingle embryo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.514\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.473\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTwo embryos\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e59.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eQuality\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c7\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e2.246\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.325\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e71.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh\u0026thinsp;+\u0026thinsp;Low\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe clinical pregnancy rate was significantly higher in the frozen embryo transfer group than the fresh group (82 patients (75.9%) vs 46 patients (44.7%) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001)), again the FET group showed a significantly higher implantation rate in comparison to the fresh group as illustrated in table (3). (30.8% vs 54.1% (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001)).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;(3): Comparison between the two studied groups according clinical pregnancy and implantation rates.\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabc\" border=\"1\"\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eFresh ET \u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;103)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eFrozen ET \u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;108)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical pregnancy rate\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e75.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.597\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of GS seen by TVU \u003c/p\u003e \u003cp\u003e(after 3\u0026ndash;5 weeks)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"2\" nameend=\"c7\" namest=\"c6\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;0.001\u003c/b\u003e\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of transferred embryos\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e159\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eImplantation rate\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e30.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e54.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eOut of the 128 pregnant females in the study, 3 pregnant patients dropped out from the fresh group, and 6 pregnant patients dropped out from the frozen group, those 9 patients were excluded from our statistical results while estimating the miscarriage rate. The miscarriage rate was higher in the fresh ET group than in the frozen ET group, however, the difference did not reach statistical significance (9 (20.9%) vs 7 (9.2%) (p\u0026thinsp;=\u0026thinsp;0.072).\u003c/p\u003e \u003cp\u003eAs for the primary outcome of the study, the ongoing pregnancy rate, out of the 211 patients included in our study, there was no available data for 9 pregnant patients, 3 patients in group 1 and 6 patients in group 2, those 9 patients were excluded from our statistical analysis while estimating the ongoing pregnancy rate. Sixty-nine patients in the frozen embryo transfer group (69/102\u0026thinsp;=\u0026thinsp;67.6%) continued their pregnancy beyond 14 weeks, while 33 patients (34/100\u0026thinsp;=\u0026thinsp;34%) of the fresh embryo transfer group continued their pregnancy beyond 14 weeks, showing a significant statistical higher ongoing pregnancy rates in the frozen embryo transfer group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Table\u0026nbsp;(4)\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;(4): Comparison between the two studied groups according to the ongoing pregnancy.\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabd\" border=\"1\"\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFresh ET\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrozen ET\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo. (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eOngoing pregnancy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;100\u003c/b\u003e\u003csup\u003e\u003cb\u003e#\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;102\u003c/b\u003e\u003csup\u003e\u003cb\u003e#\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e22.876\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (34.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69 (67.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present study showed that OPR in women with advanced endometriosis is significantly higher in the group of frozen embryo transfer compared to the fresh embryo transfer group (67.6% vs. 34% respectively). Regarding the secondary outcomes, there was a statistically significant higher implantation and clinical pregnancy rates also in the frozen embryo transfer group. To best of our knowledge, only few studies have addressed the issue of freeze all policy in women with advanced endometriosis.\u003c/p\u003e \u003cp\u003eIn agreement with the findings of the current study, Wu et al.,(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) conducted a retrospective study that encompassed 1651 women with advanced stages of endometriosis performing ICSI. After matching, 506 women and 255 women were eligible in the freeze-all group in fresh group, respectively. In their matched cohort study, the implantation, CPR and LBR were significantly higher in the FET group in comparison to the fresh groups. Those results coincide with the current study in all perspectives except for the LBR as it was not included in the outcomes for the study.\u003c/p\u003e \u003cp\u003eHowever, the present study differs from Wu et al., where in their study, the development of the embryo was accessed on day 3, and the embryos selected to be transferred were high-quality cleavage-stage embryos only (at least six blastomeres with \u0026le;\u0026thinsp;20% fragmentation based on the Cummins' Criteria). In the fresh embryo transfer group, patients were arranged for a day 3 fresh embryo transfer, and vitrification of the extra embryos. For the FET, vitrification on day 3 of the entire cohort of good quality embryos. While in the present study, embryo development was assessed on day 5 and patients performing fresh transfer were scheduled for a day-5 ET, while in the frozen group, the embryos were vitrified on day 5, and embryo transfer was not exclusively for high quality embryos, but in some cases average or low quality embryos were transferred either alone or in combination with a high quality embryo.\u003c/p\u003e \u003cp\u003eAgain the results of the present study coincided with a matched cohort prospective study conducted by Bourdon et al. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e),they compared the results of FET to fresh ET in women having endometriosis, where the FET group involved 135 women and the fresh group involved 424 matched women. CPR was of higher significance toward the FET group in comparison to the fresh group, also the ongoing pregnancy rate showed greater statistical significance in the FET group (34.8%) in comparison to the fresh-ET group (17.8%) (p\u0026thinsp;=\u0026thinsp;0.005), and the live birth rate as well was of higher significance in FET in comparison to fresh embryo transfer group.\u003c/p\u003e \u003cp\u003eAnother interesting study conducted by Mohamed et al. (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), a retrospective, database-searched cohort study. The study included two groups, the first group had freshly transferred embryos while the second group performed frozen embryo transfer. The primary outcome for the study was the live birth rate, while the secondary outcomes included the clinical pregnancy rate and the miscarriage rate. Out of the total number of cases, 415 (5.7%) had infertility attributed to endometriosis, in whom frozen ET cycles were associated with a relatively similar clinical pregnancy rate and live birth rate, in comparison to the clinical pregnancy rate and live birth rate of fresh ET cycles, showing no significant difference. Nevertheless, the study of Mohamed et al. differs from the present study as they considered other causes of infertility rather than endometriosis alone as a sole factor of infertility, it also concluded that there was no significant difference between FET over the fresh ET in cases of endometriosis concerning CPR (18.2 vs. 20.2% respectively) and LBR (16.9% vs. 15.5% respectively).\u003c/p\u003e \u003cp\u003eIn accordance, a recent systematic review and meta-analysis conducted by Chang et al. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), aimed at evaluating if FET has the ability to reimpose optimal receptivity targeting better ART results in patients with endometriosis. A total of six studies with moderate methodological quality were included in the meta-analysis. Three thousands and ten patients with endometriosis who underwent ICSI were included in the studies; 1777 performed FET, and 1233 performed fresh ET. LBR was significantly higher in the FET group in comparison to the fresh group. Although that CPR was similar between the two study groups, there was a significantly higher miscarriage rate in the fresh group.\u003c/p\u003e \u003cp\u003eThe endometrium of endometriosis-affected women is different from that of healthy, unaffected women (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), which could be the main reason for the decline in endometrial receptivity quality. Thus, it is crucial to select the right embryo transfer technique, particularly for women who have severe endometriosis. The effects of ovarian stimulation in fresh ET cycles on the early peri-implantation uterine milieu have been documented in a number of studies, three-dimensional power Doppler ultrasonography measurements have revealed that stimulated cycles have reduced endometrial and subendometrial blood flow in comparison to normal cycles (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Furthermore, certain pathologic alterations of the stimulated endometrium have been verified, such as the progression of endometrial maturation (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), as well as the early establishment of nucleolar channel systems (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAdditionally, a number of researchers have demonstrated that during fresh embryo transfer cycles, there are abnormalities in the transcriptional activity of genes related to endometrial receptivity (\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). The alterations indicated above are linked to the hyperestrogenic environment created during fresh IVF, which might subsequently hinder early embryonic adhesion (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), and consequently, the embryos' capacity to implant. It follows that the current study's findings regarding implantation, clinical pregnancy, and ongoing pregnancy are better in FET cycles.\u003c/p\u003e \u003cp\u003eOur study has the advantage of being one of the few studies that addressed the role FET in endometriosis affected women and was conducted for a fair number of patients, moreover, this study focused on advanced endometriosis being the sole factor of infertility in the studied patients, excluding any other infertility related factors, however the main study limitation was being a retrospective analysis depending on the availability of complete medical records and the follow up stopped at 14 weeks of gestation.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe present study provides affirmation that the frozen embryo transfer in cases of advanced endometriosis yields better fertility outcomes in comparison to fresh embryo transfer in terms of clinical and ongoing pregnancy rates.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eART\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eassisted reproductive technologies\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLBR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elive birth rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFET\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efrozen embryo transfer\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eASRM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAmerican Society of Reproductive Medicine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCPR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eclinical pregnancy rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOPR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eongoing pregnancy rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIVF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ein vitro fertilization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICSI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintracytoplasmic sperm injection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGnRH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003egonadotropin releasing hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAMH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eanti-mullerian hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the ethical committee of the Faculty of Medicine, Alexandria University, Egypt. No informed consent was required due to the retrospective design of the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information \u0026amp; affiliations \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHesham Adel \u0026amp; Wael El\u003cem\u003e\u0026nbsp;El Gazeirly\u003c/em\u003e are Assistant Professor of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Faculty of Medicine, Alexandria University, Egypt.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAhmed Shoukry is a Lecturer of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Faculty of Medicine, Alexandria University, Egypt\u003c/p\u003e\n\u003cp\u003eMohamed Khattab is Senior Registrar of Obstetrics and Gynecology, Alexandria University Hospitals, Egypt.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContribution\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eHesham Adel\u003c/em\u003e \u0026amp; \u003cem\u003eAhmed\u003c/em\u003e \u003cem\u003eShoukry\u003c/em\u003e were the main authors responsible of the research and writing the paper.\u0026nbsp;\u003cem\u003eMohamed Khattab\u003c/em\u003e was responsible for the data collection,\u0026nbsp;\u003cem\u003eWael El Gazeirly\u0026nbsp;\u003c/em\u003ewas responsible for reviewing and revising the paper. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no external funds.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eZegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, De Mouzon J, Sokol R, Cooke ID (2017) The international glossary on infertility and fertility care, 2017. 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Endocrinology 144(7):2870\u0026ndash;2881\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCanis M, Donnez JG, Guzick DS, Halme JK, Rock JA, Schenken RS, Vernon MW (1997) Revised american society for reproductive medicine classification of endometriosis. Fertil Steril 67(5):817\u0026ndash;821\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu J, Yang X, Huang J, Kuang Y, Wang Y (2019) Fertility and Neonatal Outcomes of Freeze-All vs. Fresh Embryo Transfer in Women With Advanced Endometriosis. Front Endocrinol 10:770\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBourdon M, Santulli P, Maignien C, Gayet V, Pocate-Cheriet K, Marcellin L, Chapron C (2018) The deferred embryo transfer strategy improves cumulative pregnancy rates in endometriosis-related infertility: A retrospective matched cohort study. PLoS ONE, 13(4), e0194800\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohamed AM, Chouliaras S, Jones CJ, Nardo LG (2011) Live birth rate in fresh and frozen embryo transfer cycles in women with endometriosis. Eur J Obstet Gynecol Reprod Biol 156(2):177\u0026ndash;180\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang Y, Shen M, Wang S, Li X, Duan H (2022) Association of embryo transfer type with infertility in endometriosis: a systematic review and meta-analysis. J Assist Reprod Genet 39(5):1033\u0026ndash;1043\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMirkin S, Nikas G, Hsiu J-G, D\u0026iacute;az J, Oehninger S (2004) Gene expression profiles and structural/functional features of the peri-implantation endometrium in natural and gonadotropin-stimulated cycles. J Clin Endocrinol Metab 89(11):5742\u0026ndash;5752\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHorcajadas JA, Riesewijk A, Polman J, van Os R, Pellicer A, Mosselman S, Sim\u0026oacute;n C (2004) Effect of controlled ovarian hyperstimulation in IVF on endometrial gene expression profiles. Mol Hum Reprod 11(3):195\u0026ndash;205\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaouzi D, Assou S, Mahmoud K, Tondeur S, R\u0026egrave;me T, Hedon B, Hamamah S (2009) Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients. HumReprod 24(6):1436\u0026ndash;1445\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValbuena D, Martin J, de Pablo JL, Remohı́ J, Pellicer A, Sim\u0026oacute;n C (2001) Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo. Fertil Steril 76(5):962\u0026ndash;968\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":"middle-east-fertility-society-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mefj","sideBox":"Learn more about [High Temperature Corrosion of Materials](https://www.springer.com/journal/43043)","snPcode":"43043","submissionUrl":"https://submission.nature.com/new-submission/43043/3","title":"Middle East Fertility Society Journal","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"endometriosis, freeze all, frozen embryo transfer, ongoing pregnancy rate","lastPublishedDoi":"10.21203/rs.3.rs-4335275/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4335275/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e \u003c/strong\u003eART in women with\u003cstrong\u003e \u003c/strong\u003eendometriosis is associated with poor quality of the retrieved oocytes and lower fertilization and pregnancy rates, reflecting that endometriosis may influence fertility by altering the quality of both the oocyte and embryo quality and also by impairing the endometrial receptivity. On comparing endometriosis affected patients to healthy counterparts, many differences were demonstrated at the endometrial level. Thus, choosing the appropriate method of embryo transfer is of utmost importance, particularly for patients with advanced endometriosis. \u003cem\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e\u003c/em\u003e The aim of the present study was to compare the reproductive outcomes between fresh and frozen embryo transfer cycles in women with advanced endometriosis. A retrospective cohort study was conducted for patients recruited from two IVF centers, Alexandria, Egypt. Careful review of paper and electronic medical records of infertile women (primary, relative, or secondary infertility) aged 18 – 37 years who were diagnosed with advanced endometriosis by means of laparoscopy and were scheduled for ICSI followed by either fresh embryo transfer (group I) or freeze all embryos and deferred embryo transfer (group II) of day 5 embryo(s) were included in the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e:\u003c/em\u003e Two hundred and eleven women were eligible and included in the study. Women in each study group were matched regarding baseline characteristics. Clinical pregnancy, implantation, ongoing pregnancy rates were statistically significant higher in the group of frozen embryo transfer (p\u0026lt;0.001). Miscarriage rate was found to be higher in the group of fresh transfer compared to FET group but without a statistical significance (20.9% vs 9.2%, p = 0.072).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/em\u003e In women with advanced endometriosis, freeze all policy is associated with better implantation, ongoing pregnancy rates and it is recommended to be adopted when appropriate in such patients.\u003c/p\u003e","manuscriptTitle":"Reproductive outcomes in women with advanced endometriosis in fresh versus frozen embryo transfer cycles.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-30 18:43:53","doi":"10.21203/rs.3.rs-4335275/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-05-15T10:07:28+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-14T22:04:36+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Middle East Fertility Society Journal","date":"2024-05-11T10:01:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-29T07:06:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"Middle East Fertility Society Journal","date":"2024-04-27T15:19:34+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"middle-east-fertility-society-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mefj","sideBox":"Learn more about [High Temperature Corrosion of Materials](https://www.springer.com/journal/43043)","snPcode":"43043","submissionUrl":"https://submission.nature.com/new-submission/43043/3","title":"Middle East Fertility Society Journal","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"81affd4b-4411-4ba1-b234-e17908603abe","owner":[],"postedDate":"May 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-12T16:06:22+00:00","versionOfRecord":{"articleIdentity":"rs-4335275","link":"https://doi.org/10.1186/s43043-024-00200-x","journal":{"identity":"middle-east-fertility-society-journal","isVorOnly":false,"title":"Middle East Fertility Society Journal"},"publishedOn":"2024-08-08 15:58:10","publishedOnDateReadable":"August 8th, 2024"},"versionCreatedAt":"2024-05-30 18:43:53","video":"","vorDoi":"10.1186/s43043-024-00200-x","vorDoiUrl":"https://doi.org/10.1186/s43043-024-00200-x","workflowStages":[]},"version":"v1","identity":"rs-4335275","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4335275","identity":"rs-4335275","version":["v1"]},"buildId":"B-jG_2CBjPDmsCi4Wdhf-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}