Search

Research Question: What is the association between endometrial thickness (EMT) and the birthweight of singleton infants born from frozen-thawed embryo transfer cycles?, Design: This retrospective cohort study was conducted from January 2016 to December 2019. Participants were categorized into a natural cycle (NC, n = 8132) group and hormone replacement therapy (HRT, n = 4975) group. Only singleton deliveries were included. The primary outcomes were measures of birthweight and relevant indexes. Multivariable logistic regression and multivariable-adjusted linear regression models that incorporated restricted cubic splines were used., Results: In the HRT group, the risk of delivering a small for gestational age (SGA) infant was increased in women with an EMT <8.0 mm (adjusted odds ratio [aOR] 1.85, 95% confidence interval [CI] 1.17-2.91) compared with women with an EMT of 8.0 to <12.0 mm, and increased with an EMT ≥12.0 mm (aOR 1.85, 95% CI 1.03-3.33). An inverted U-shaped relationship was found between EMT and birthweight in women with HRT. No significant differences were shown in birthweight z-score, or being SGA or large for gestational age, in singletons among the three EMT groups in the natural cycles., Conclusions: A thinner endometrium seen in women undergoing HRT cycles was associated with a lower birthweight z-score, as well as a higher risk of SGA. However, no significant association was observed between EMT and birthweight z-score or SGA in the NC group. It is noteworthy that a thicker endometrium was not associated with a higher birthweight in frozen-thawed embryo transfer (FET) cycles. Women with a thin endometrium who achieve pregnancy require specialized attention, particularly if they are undergoing FET with HRT cycles., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate variations in pregnancy outcomes between preimplantation genetic testing for aneuploidy (PGT-A) and conventional in vitro fertilization and embryo transfer (IVF-ET) treatment across distinct groups categorized by oocyte and blastocyst counts. Because the live birth rate (LBR) of assisted reproductive technology treatment is influenced by the number of oocytes and blastocysts retrieved. Our previous study indicated comparable cumulative LBRs (CLBRs) between conventional IVF-ET and PGT-A., Design: A post hoc exploratory secondary analysis of data from a multicenter randomized controlled trial compared the CLBRs between conventional IVF-ET and PGT-A., Setting: Academic fertility centers., Subjects: A total of 1,212 infertile women with a good prognosis for a live birth after PGT-A or conventional IVF-ET were included., Intervention: Women underwent PGT-A or conventional IVF-ET., Main Outcome Measure(s): Cumulative LBR, cumulative clinical pregnancy loss (CPL) rate, and good birth outcome., Result(s): In the study, all participants were divided into 4 groups on the basis of quartiles of the number of oocytes retrieved, or blastocysts. There was an interaction between whether to perform PGT-A and the oocyte numbers category on cumulative CPL and biochemical pregnancy loss. Chi-square analysis revealed that the PGT-A group showed a lower cumulative frequency of CPL compared with the IVF-ET group (PGT-A vs. IVF-ET: 5.9% vs. 13.7%; relative risk = 0.430; 95% confidence interval, 0.243-0.763) when the number of oocytes retrieved was <15. Although there was no interaction on CLBR when the retrieved oocyte count ranged from 19-23 (19≤ oocytes <23) the PGT-A group exhibited a lower CLBR than the conventional IVF-ET group (PGT-A vs IVF-ET: 75.6% vs 87.1%; relative risk = 0.868; 95% confidence interval, 0.774-0.973), and the average body weight of newborns from the PGT-A group was approximately 142 g lower than that of the conventional IVF-ET group (PGT-A vs. IVF-ET: 3,334 ± 479 g vs. 3,476 ± 473 g). However, no statistically significant difference in the CLBR was observed between the PGT-A and IVF-ET groups in the other oocyte or blastocyst groups., Conclusion: When the number of retrieved eggs was <15, the PGT-A group exhibited a lower cumulative CPL rate but no higher CLBR than the conventional IVF-ET group., Clinical Trial Registration Number: NCT03118141., Competing Interests: Declaration of Interests M.H. has nothing to disclose. M.L. has nothing to disclose. S.T. has nothing to disclose. L.G. has nothing to disclose. Z.Z. has nothing to disclose. Z-J.C. has nothing to disclose. Y.L. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Frozen embryo transfer (FET) has become a widely employed assisted reproductive technology technique. There have historically been concerns regarding the long-term metabolic safety of FET technology in offspring due to pregnancy-induced hypertension and large for gestational age, both of which are well-recognized factors for metabolic dysfunction of children. Therefore, we aimed to compare the metabolic profiles of children born after frozen versus fresh embryo transfer at 2 to 5 years of age., Methods and Findings: This was a prospective cohort study. Using data from the "Assisted Reproductive Technology borned KIDs (ARTKID)," a birth cohort of offspring born from assisted reproductive technology at the Institute of Women, Children and Reproductive Health, Shandong University, China. We included 4,246 singletons born after FET (n = 2,181) and fresh embryo transfer (n = 2,065) enrolled between 2008 and 2019 and assessed the glucose and lipid variables until the age of 2 to 5 years. During a mean follow-up of 3.6 years, no significant differences were observed in fasting blood glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance Index, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol levels between offspring conceived by fresh and frozen embryo transfer in the crude model and adjusted model (adjusted for parental age, parental body mass index, parental education level, paternal smoking, parity, offspring age and sex). These results remained consistent across subgroup analyses considering offspring age, the stage of embryo transfer, and the mode of fertilization. Results from sensitivity analysis on children matched for age within the cohort remains the same. The main limitation of our study is the young age of the offspring., Conclusions: In this study, the impact of FET on glucose and lipid profiles during early childhood was comparable to fresh embryo transfer. Long-term studies are needed to evaluate the metabolic health of offspring born after FET., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Over the past decade, the application of frozen-thawed embryo transfer treatment cycles has increased substantially. Hormone replacement therapy and the natural cycle are two popular methods for preparing the endometrium. Hormone replacement therapy is now used at the discretion of the doctors because it is easy to coordinate the timing of embryo thawing and transfer with the schedules of the in-vitro fertilization lab, the treating doctors, and the patient. However, current results suggest that establishing a pregnancy in the absence of a corpus luteum as a result of anovulation may pose significant maternal and fetal risks. Therefore, a 'back to nature' approach that advocates an expanded use of natural cycle FET in ovulatory women has been suggested. Currently, there is increasing interest in how the method of endometrial preparation may influence frozen embryo transfer outcomes specifically, especially when it comes to details such as different types of ovulation monitoring and different luteal support in natural cycles, and the ideal exogenous hormone administration route as well as the endocrine monitoring in hormone replacement cycles. In addition to improving implantation rates and ensuring the safety of the fetus, addressing these points will allow for individualized endometrial preparation, also as few cycles as possible would be canceled., (© 2023. The Author(s).)

Introduction: Existing randomised controlled trials (RCTs) comparing a freeze-all embryo transfer strategy and a fresh embryo transfer strategy have shown conflicting results. A freeze-all or a fresh transfer policy may be preferable for some couples undergoing in-vitro fertilisation (IVF), but it is unclear which couples would benefit most from each policy, how and under which protocols. Therefore, we plan a systematic review and individual participant data meta-analysis of RCTs comparing a freeze-all and a fresh transfer policy., Methods and Analysis: We will search electronic databases (Medline, Embase, PsycINFO and CENTRAL) and trial registries (ClinicalTrials.gov and the International Clinical Trials Registry Platform) from their inception to present to identify eligible RCTs. We will also check reference lists of relevant papers. The search was performed on 23 September 2020 and will be updated. We will include RCTs comparing a freeze-all embryo transfer strategy and a fresh embryo transfer strategy in couples undergoing IVF. The primary outcome will be live birth resulting from the first embryo transfer. All outcomes listed in the core outcome set for infertility research will be reported. We will invite the lead investigators of eligible trials to join the In dividual participant data meta-analysis of trials comparing f r o zen versus f r esh e m bryo transfer strategy (INFORM) collaboration and share the deidentified individual participant data (IPD) of their trials. We will harmonise the IPD and perform a two-stage meta-analysis and examine treatment-covariate interactions for important baseline characteristics., Ethics and Dissemination: The study ethics have been granted by the Monash University Human Research Ethics Committee (Project ID: 30391). The findings will be disseminated via presentations at international conferences and publication in peer-reviewed journals., Prospero Registration Number: CRD42021296566., Competing Interests: Competing interests: RW reports grants from the NHMRC and NHMRC Centre for Research Excellence in Women's Health in Reproductive Life (CRE WHiRL). LNV reports personal fees from Merck, Merck Sharpe and Dohme, Ferring, outside the submitted work. AP reports grants and personal fees from Gedeon Richter, Ferring Pharmaceuticals and Merck A/S and personal fees from IBSA, outside the submitted work. CB reports grants and personal fees from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S and Organon, and personal fees from IBSA and Abbott outside the submitted work. CS is a co-inventor of Igenomix SL and Head of Scientific Advisory Board at Igenomix SL. BWM is supported by a NHMRC Investigator grant (GNT1176437). BWM reports personal fees from ObsEva and Merck, and travel support from Merck, outside the submitted work. SB is the Editor in Chief of Human Reproduction Open. AM reports grants from HTA/NIHR, travel/meeting support from Ferring and Pharmasure and participation in a Ferring advisory board. All other authors do not have competing interests to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess whether the between-group difference in singleton birth weight following frozen vs. fresh embryo transfer varied with infant sex., Design: A post hoc exploratory secondary analysis of data from three multicenter randomized trials compared the live birth rates between freeze-only vs. fresh embryo transfer., Setting: Academic fertility centers., Patient(s): A total of 1,886 women who achieved singleton live birth after a frozen or fresh embryo transfer during these trials were included., Intervention(s): Women underwent either a frozen or fresh embryo transfer., Main Outcome Measure(s): Mean birth weight, large for gestational age (LGA), and small for gestational age (SGA)., Result(s): There was an interaction between the types of embryo transfer and infant sex on the birth weight and on the incidences of LGA and SGA. Among male infants, compared with singletons following fresh embryo transfer, singletons following frozen embryo transfer had higher mean birth weights (3,520.6 ± 526.1 vs. 3,345.1 ± 524.9 g), a higher risk of being LGA (25.2% vs. 15.7%), and a lower risk of being SGA (3.3% vs. 6.1%). However, among the female infants, no statistically significant difference was found in the mean birth weight (3,336.5 ± 514.8 vs. 3,299.5 ± 485.0 g) or the risks of being LGA (18.8% vs. 15.7%) or SGA (5.2% vs. 6.0%) between frozen and fresh embryo transfer., Conclusion(s): Male singletons born after frozen embryo transfer were more likely to have a higher birth weight than those born after fresh embryo transfer., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Frozen embryo transfer is associated with a higher rate of live birth and a lower risk for ovarian hyperstimulation syndrome in women with polycystic ovary syndrome (PCOS) compared with fresh embryo transfer. The aim of this study is to assess the optimal endometrial preparation protocol for women with PCOS undergoing frozen embryo transfer., Material and Methods: We conducted a historical cohort analysis of 1720 women with PCOS who underwent the "freeze-all" strategy between August 2014 and August 2017 because of their high risk for ovarian hyperstimulation syndrome. Three endometrial preparation protocols were used: natural cycle (NC; n = 191), which relies on the dominant follicle to secrete estrogen that then promotes endometrial growth; ovarian stimulation (OS; n = 96), which induces follicle growth using low doses of human menopausal gonadotropin; and hormone replacement (HRT; n = 1433), which uses exogenous estradiol to promote endometrial growth. The primary outcome was live birth., Results: For women who received a single embryo transfer, the live birth rates for the NC, OS, and HRT groups were 62.4%, 65.0%, and 52.2%, respectively. The live birth rate in the HRT group was significantly lower than that seen in the OS and NC groups (P = .009). The clinical pregnancy rates of the three groups were 72.3%, 73.8%, and 64.9%, respectively; this difference did not reach statistical significance (P = .071)., Conclusions: The rate of live birth with the NC and OS regimens was higher than with the HRT protocol in women with PCOS who undergo single-blastocyst frozen embryo transfer., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology.)

Research Question: Is there a difference in live birth rate between a freeze-only strategy and fresh embryo transfer, and what is the effect of varying progesterone concentrations on the day of human chorionic gonadotrophin (HCG) administration?, Design: A secondary analysis of data from three randomized trials comparing the live birth rate after elective frozen versus fresh embryo transfer, which respectively enrolled 1508 women with polycystic ovary syndrome, 2157 ovulatory women who underwent cleavage-stage embryo transfer and 1650 ovulatory women who underwent single blastocyst transfer. Women were randomly assigned to the frozen or fresh embryo transfer group in the original trials. The primary outcome was live birth rate after the initial embryo transfer., Results: The live birth rate after a freeze-only strategy was consistently higher than fresh embryo transfer at any progesterone concentration on the day of HCG administration. Nonetheless, the between-group difference in live birth rate after frozen versus fresh embryo transfer was greater in women with progesterone concentrations ≥1.14 ng/ml (52.7% versus 37.3%, odds ratio (OR) 1.88, 95% confidence interval (CI) 1.55-2.27, P = 7.89  ×  10 -11 ) than in women with progesterone concentrations <1.14 ng/ml (53.3% versus 48.1%, OR 1.23, 95% CI 1.08-1.41, P = 0.002). In women with progesterone concentration ≥1.14 ng/ml, frozen embryo transfer also resulted in higher rates of conception and clinical pregnancy than fresh embryo transfer., Conclusion: In women with normal or high ovarian response, a freeze-only strategy resulted in a higher live birth rate than fresh embryo transfer, irrespective of progesterone concentration. Moreover, women with progesterone concentration ≥1.14 ng/ml may benefit more from a freeze-only strategy., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Recurrent implantation failure (RIF) brings great challenges to clinicians and causes deep frustration to patients. Previous data has suggested that prednisone may play a promising role in the establishment of pregnancy and help improve the pregnancy outcome in women with RIF. But there is insufficient evidence from randomized clinical trials that had adequate power to determine if prednisone can enhance live births as the primary outcome., Methods/design: This trial is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial (1:1 ratio of prednisone versus placebo). Infertile patients with RIF who intend to undergo frozen-thawed embryo transfer (FET) after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) or pre-implantation genetic testing for aneuploidy (PGT-A) will be enrolled and randomly assigned to two parallel groups. Participants will be given the treatment of prednisone or placebo from the start of endometrial preparation till the end of the first trimester of pregnancy if pregnant. The primary outcome is live birth rate., Discussion: The results of this study will provide evidence for the effect of prednisone on pregnancy outcomes in patients with RIF., Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800018783 . Registered on 9 October 2018.

Purpose: Mosaicism is a prevalent characteristic of human preimplantation embryos. This retrospective cohort study aimed to investigate pregnancy outcomes after transfer of mosaic or euploid embryos., Methods: The embryos, which had been transferred as "euploidy," were processed using array-based comparative genomic hybridization (aCGH). The original aCGH charts of the transferred embryos were reanalyzed. Mosaic and control euploid embryos were defined according to log2 ratio calls., Results: Overall, 102 embryos were determined to be mosaic, of which 101 were estimated to harbor no more than 50% aneuploid mosaicism. Additionally, 268 euploid embryos were matched as controls. The rates of live birth (46.6% vs. 59.1%, odds ratio (OR) 0.60, 95% confidence interval (CI) 0.38-0.95), and biochemical pregnancy (65.7% vs. 76.1%, OR 0.60, 95% CI 0.37-0.99) per transfer cycle were significantly lower after mosaic embryo transfer than after euploid embryo transfer. The rates of clinical pregnancy and pregnancy loss and the risks of obstetric outcomes did not differ significantly between the two groups., Conclusions: Compared with euploid embryo transfer, mosaic embryo transfer is associated with a lower rate of live birth, which is mainly attributed to a decreased rate of conception. However, as mosaic embryo transfer yielded a live birth rate of 46.6%, patients without euploid embryos could be counseled regarding this alternative option.

Context: Supraphysiological estradiol exposure after ovarian stimulation may disrupt embryo implantation after fresh embryo transfer. Women with polycystic ovary syndrome (PCOS), who usually overrespond to ovarian stimulation, have a better live birth rate after frozen embryo transfer (FET) than after fresh embryo transfer; however, ovulatory women do not., Objective: To evaluate whether the discrepancy in live birth rate after fresh embryo transfer vs FET between these two populations is due to the variation in ovarian response (i.e., peak estradiol level or oocyte number)., Design, Setting, Patients, Intervention(s), and Main Outcome Measure(s): This was a secondary analysis of data from two multicenter randomized trials with similar study designs. A total of 1508 women with PCOS and 2157 ovulatory women were randomly assigned to undergo fresh or FET. The primary outcome was live birth., Results: Compared with fresh embryo transfer, FET resulted in a higher live birth rate (51.9% vs 40.7%; OR, 1.57; 95% CI, 1.22 to 2.03) in PCOS women with peak estradiol level >3000pg/mL but not in those with estradiol level ≤3000 pg/mL. In women with PCOS who have ≥16 oocytes, FET yielded a higher live birth rate (54.8% vs 42.1%; OR, 1.67; 95% CI, 1.20 to 2.31), but this was not seen in those with <16 oocytes. In ovulatory women, pregnancy outcomes were similar after fresh embryo transfer and FET in all subgroups., Conclusions: Supraphysiological estradiol after ovarian stimulation may adversely affect pregnancy outcomes in women with PCOS but not in ovulatory women.

Tamoxifen has played a vital role in endocrine therapy for the treatment of estrogen receptor-positive breast cancer. We examined the effect of tamoxifen in patients with a thin endometrium in frozen-thawed embryo transfer (FET) cycles and compared the improvement in endometrial thickness (EMT) and pregnancy outcomes stratified by different etiologies of thin endometrium. A total of 226 women were recruited for a new tamoxifen protocol; all had an EMT of less than 7.5 mm in previous cycles, including natural cycle (NC), hormone replacement treatment (HRT), and ovulation induction (OI) cycles. Compared with previous cycles, tamoxifen cycles showed a significantly increased EMT (from 6.11 ± 0.98 mm to 7.87 ± 1.48 mm in the NC group, from 6.24 ± 1.01 mm to 8.22 ± 1.67 mm in the HRT group, and from 6.34 ± 1.03 mm to 8.05 ± 1.58 mm in the OI group; all P < .001). Patients were further divided into 3 groups based on the causes of their thin endometrium: (1) history of intrauterine adhesion (n = 34), (2) history of uterine curettage (n = 141), and (3) polycystic ovary syndrome (PCOS; n = 51). Patients with PCOS obtained the thickest EMT (9.31 ± 1.55 mm), the lowest cycle cancellation rate (11.76%), and the highest rate of clinical pregnancy (60%) and live birth (55.56%) per transfer ( P < .001). Multivariable regression analysis showed that EMT was related to live birth (odds ratio: 1.487; 95% confidence interval: 1.172-1.887). A tamoxifen protocol improves EMT in patients after NC, HRT, and OI cycles during FET. Patients with PCOS show the most benefit from tamoxifen and achieve better pregnancy outcomes.

Objective: To evaluate the effect of frozen embryo transfer on maternal and neonatal complications of singleton and twin pregnancies compared with fresh embryo transfer in women with polycystic ovary syndrome (PCOS)., Design: A secondary analysis of a multicenter, randomized, controlled trial comparing live birth after frozen vs. fresh embryo transfer (FreFro-PCOS)., Setting: Reproductive medicine centers., Patient(s): A total of 1,508 patients with a diagnosis of PCOS who were undergoing IVF were enrolled., Intervention(s): On day of oocyte retrieval, eligible patients were randomized to the fresh or frozen embryo transfer groups. Up to two embryos were transferred in both groups. All pregnancies were followed up until delivery., Main Outcome Measure(s): Gestational diabetes mellitus, pre-eclampsia, preterm birth, small for gestational age, and large for gestational age., Result(s): The risks of gestational diabetes mellitus, preterm birth, and small for gestational age were comparable between the frozen and fresh embryo transfer groups in both singleton and twin births. However, singleton infants born after frozen embryo transfer were more likely to be large for gestational age (25.2% vs. 17.5%; relative risk 1.44, 95% confidence interval 1.01-2.07, P=.044) than those born after fresh embryo transfer. Twin pregnancy after frozen embryo transfer had a higher risk of pre-eclampsia (12.0% vs. 2.8%; relative risk 4.31, 95% confidence interval 1.27-14.58, P=.009) than those after fresh embryo transfer., Conclusion(s): In women with PCOS, frozen embryo transfer resulted in an increased risk of large for gestational age in singleton pregnancy and a higher risk of pre-eclampsia in twin pregnancy., Clinical Trial Registration Number: NCT01841528., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Elective frozen-embryo transfer has been shown to result in a higher live-birth rate than fresh-embryo transfer among anovulatory women with the polycystic ovary syndrome. It is uncertain whether frozen-embryo transfer increases live-birth rates among ovulatory women with infertility., Methods: In this multicenter, randomized trial, we randomly assigned 2157 women who were undergoing their first in vitro fertilization cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. Up to two cleavage-stage embryos were transferred in each participant. The primary outcome was a live birth after the first embryo transfer., Results: The live-birth rate did not differ significantly between the frozen-embryo group and the fresh-embryo group (48.7% and 50.2%, respectively; relative risk, 0.97; 95% confidence interval [CI], 0.89 to 1.06; P=0.50). There were also no significant between-group differences in the rates of implantation, clinical pregnancy, overall pregnancy loss, and ongoing pregnancy. Frozen-embryo transfer resulted in a significantly lower risk of the ovarian hyperstimulation syndrome than fresh-embryo transfer (0.6% vs. 2.0%; relative risk, 0.32; 95% CI, 0.14 to 0.74; P=0.005). The risks of obstetrical and neonatal complications and other adverse outcomes did not differ significantly between the two groups., Conclusions: The live-birth rate did not differ significantly between fresh-embryo transfer and frozen-embryo transfer among ovulatory women with infertility, but frozen-embryo transfer resulted in a lower risk of the ovarian hyperstimulation syndrome. (Funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China; Chinese Clinical Trial Registry number, ChiCTR-IOR-14005406 .).

Competing Interests: Conflict of Interest: All authors stated no conflict of interest.

Objective: To compare the risk of ectopic pregnancy (EP) after embryo transfer on day 3(D3-ET) and day 5(D5-ET)., Design: Meta-analysis., Patients: Women with pregnancy resulting from in vitro undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)., Result(s): Twenty-two studies were identified through research conducted using the PubMed, Embase, and Cochrane databases and ClinicalTrials.gov. All studies were conducted prior to October 2016. Adding the reproductive data from our center, a total of 143 643 pregnancies were reviewed(D3-ET: n = 62027,D5-ET:n = 81616). A lower EP rate was found in women undergoing D5-ET than in those undergoing D3-ET [relative risk (RR), 0.67;95% confidence interval (CI), 0.54-0.85;143643 pregnancies in 23 studies; I2 = 67%]. These results were validated in subgroups of fresh embryo-transfer (Fre-ET) cycles [RR, 0.78; 95%CI, 0.69-0.88; 91 871 pregnancies in 21 studies; I2 = 29%] and frozen-thawed embryo-transfer (Fro-ET) cycles [RR, 0.43; 95%CI, 0.36-0.51; 51 772 pregnancies in 10 studies; I2 = 33%]. After separating out the randomized controlled trials (RCTs), a significant difference was found in the retrospective studies in both subgroups [both Fre-ET (RR,0.78;95% CI 0.69-0.88);91182 pregnancies in 14 studies; I2 = 45%] and Fro-ET(RR,0.43;95% CI 0.36-0.51; 51751pregnancies in 9 studies;I2 = 33%)], while the RCTs showed no statistical significance for Fre-ET cycles[RR,0.86;95% CI 0.32-2.26); 689 pregnancies in 7 studies; I2 = 0%]., Conclusion(s): The present study indicates that D5-ET reduces the risk for EP in cycles that use IVF or ICSI, compared with D3-ET. It suggests that D5-ET may be a better choice for decreasing the EP rate in assisted reproductive technology. Further high-quality randomized controlled trials are anticipated., Competing Interests: The authors have declared that no competing interests exist.

Background: The transfer of fresh embryos is generally preferred over the transfer of frozen embryos for in vitro fertilization (IVF), but some evidence suggests that frozen-embryo transfer may improve the live-birth rate and lower the rates of the ovarian hyperstimulation syndrome and pregnancy complications in women with the polycystic ovary syndrome., Methods: In this multicenter trial, we randomly assigned 1508 infertile women with the polycystic ovary syndrome who were undergoing their first IVF cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. After 3 days of embryo development, women underwent the transfer of up to two fresh or frozen embryos. The primary outcome was a live birth after the first embryo transfer., Results: Frozen-embryo transfer resulted in a higher frequency of live birth after the first transfer than did fresh-embryo transfer (49.3% vs. 42.0%), for a rate ratio of 1.17 (95% confidence interval [CI], 1.05 to 1.31; P=0.004). Women who underwent frozen-embryo transfer also had a lower frequency of pregnancy loss (22.0% vs. 32.7%), for a rate ratio of 0.67 (95% CI, 0.54 to 0.83; P<0.001), and of the ovarian hyperstimulation syndrome (1.3% vs. 7.1%), for a rate ratio of 0.19 (95% CI, 0.10 to 0.37; P<0.001), but a higher frequency of preeclampsia (4.4% vs. 1.4%), for a rate ratio of 3.12 (95% CI, 1.26 to 7.73; P=0.009). There were no significant between-group differences in rates of other pregnancy and neonatal complications. There were five neonatal deaths in the frozen-embryo group and none in the fresh-embryo group (P=0.06)., Conclusions: Among infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth, a lower risk of the ovarian hyperstimulation syndrome, and a higher risk of preeclampsia after the first transfer than was fresh-embryo transfer. (Funded by the National Basic Research Program of China and others; ClinicalTrials.gov number, NCT01841528.).

Purpose: To investigate whether intracavitary physiotherapy is superior to endometrial scratching in patients with recurrent implantation failure (RIF) after in vitro fertilization/intracytoplasmic sperm injection- embryo transfer (IVF/ICSI-ET) cycles., Methods: According to the inclusion criteria defined by our hospital, 63 patients with RIF were included in the retrospective study. 20 patients who received intracavitary physiotherapy were classified into Group A, 8 patients with both intracavitary physiotherapy and endometrial scratching were into Group B, and 35 patients who underwent endometrial scratching were into Group C. The primary outcome measures were implantation and clinical pregnancy rates. The secondary outcome measure was pregnancy outcome., Results: There were no statistical differences in implantation and clinical pregnancy rates between Groups A and C (29.41 vs 35.59 %, 45.00 vs 48.57 % respectively, P > 0.05), Groups B and C (36.36 vs 35.59 %, 50.00 vs 48.57 % respectively, P > 0.05). In addition, no statistical differences were discovered in pregnancy outcomes between Groups A and C (P > 0.05), Groups B and C (P > 0.05)., Conclusions: Intracavitary physiotherapy is not inferior to endometrial scratching on improving implantation and clinical pregnancy rates in patients with RIF after IVF/ICSI cycles.

Background: Polycystic ovary syndrome (PCOS) patients are at increased risk of pregnancy complications, which may impair pregnancy outcome. Transfer of fresh embryos after superovulation may lead to abnormal implantation and placentation and further increase risk for pregnancy loss and complications. Some preliminary data suggest that elective embryo cryopreservation followed by frozen-thawed embryo transfer into a hormonally primed endometrium could result in a higher clinical pregnancy rate than that achieved by fresh embryo transfer., Methods/design: This study is a multicenter, prospective, randomized controlled clinical trial (1:1 treatment ratio of fresh vs. elective frozen embryo transfers).. A total of 1,180 infertile PCOS patients undergoing the first cycle of in vitro fertilization (IVF) or intracytoplasmic sperm injection will be enrolled and randomized into two parallel groups. Participants in group A will undergo fresh embryo transfer on day 3 after oocyte retrieval, and participants in group B will undergo elective embryo cryopreservation after oocyte retrieval and frozen-thawed embryo transfer in programmed cycles. The primary outcome is the live birth rate. Our study is powered at 80 to detect an absolute difference of 10 at the significance level of 0.01 based on a two-sided test., Discussion: We hypothesize that elective embryo cryopreservation and frozen-thawed embryo transfer will reduce the incidence of pregnancy complications and increase the live birth rate in PCOS patients who need IVF to achieve pregnancy., Trial Registration: ClinicalTrials.gov Identifier: NCT01841528.

Background: Embryo quality and receptivity of the endometrium are two factors that determine the results of in vitro fertilization/intra-cytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). There is no consensus of the optimal transfer strategy for normal responders or high responders. The current study aimed to find the optimal transfer strategy for different subgroups of patients., Methods: From April 2010 to December 2010, patients who meet the following criteria were included in this study; primary infertility, female age ≤ 35 years, FSH level on female cycle day 2 - 3 ≤ 12 mIU/ml, at least six good quality embryos available on day three. The clinical outcomes using different transfer strategies between normal responders and high responders were reviewed and compared., Results: For the normal responders, the clinical pregnancy rate of day three double-embryo transfer (DET) was comparable to that of day five elective single blastocyst transfer (eSBT), 64.04% vs. 60.33% (P > 0.05). For the high responders, the clinical pregnancy rate of day five eSBT was significantly lower than that of day three DET, 43.35% vs. 57.21% (P < 0.05). For the high responders, the rates of clinical pregnancy and implantation in frozen-thawed embryo transfer (FET) cycles were notably higher than in eSBT cycles (64.56% vs. 43.35% and 62.11% vs. 43.35% respectively) (P < 0.05)., Conclusions: For normal responders, eSBT might be an applicable strategy to reduce multiple pregnancy rates while maintaining acceptable overall pregnancy rates. And in order to reduce multiple pregnancies and increase the chance of pregnancy of high responders, FET may be a preferable strategy.

This is a retrospective, observational study to evaluate the effect of maternal age on the outcomes of in vitro fertilization and embryo transfer (IVF-ET). 11830 IVF-ET cycles from 10268 women were included. Four groups of different maternal age periods were compared. The groups were 21-30 years old group (4549 cycles), 31-35 years old group (4424 cycles), 36-40 years old group (2429 cycles), and over 40 years old group (428 cycles). The mean starting dose of Gn and mean total dose of Gn in each cycle were significantly higher (P<0.01), while the mean retrieved oocyte number was significantly lower (P<0.01) in groups of higher maternal age period than those in each of the lower groups. The biochemical pregnancy rate and the clinical pregnancy rate were significantly lower (P<0.01), while the miscarriage rate was significantly higher (P<0.01) in groups of higher maternal age period than those in the lower groups. No difference was found in two-pronuclear zygotes (2PN) rate and good quality embryo rate among different groups. Birth defect rate was also comparable in the born babies in different groups. In the group with patients' age over 40 years old, the pregnancy rate was 26.87%, the clinical pregnancy rate was 19.39%, while the miscarriage rate after clinical pregnancy was 36.14%. To draw the conclusion, patients with higher maternal age had worse IVF outcomes. In women of fertile age, patients between 20 and 30 years old have the best IVF outcomes. Patients over 40 years old have poor IVF outcome and high miscarriage rate, which suggested the necessity of preimplantation genetic screening (PGS).

The purpose of this study was to explore the effects of cumulus cells on vitreous cryopreservation of human mature oocytes and clinical pregnancy outcomes. The study was divided into group A (cumulus cells were removed from the oocytes before freezing) containing 24 participants and 193 oocytes and group B (cumulus cells were retained with the oocytes before freezing) containing 26 participants and 240 oocytes. Based on no significant differences in age, duration of infertility, infertile causes, and number of retrieved oocytes between both groups when oocytes were retrieved from infertile women, we found that the survival rate of post thaw oocytes (88% vs 58%), cleavage rate (80% vs 56%), and high-quality embryo rate (75% vs 59%) were significantly higher in group B than in group A. Under the conditions that there were no significant differences between the 2 groups in the general status of the participants undergoing embryo transfer, the embryo implantation rate (37% vs 15%) and the clinical pregnancy rate (50% vs 17%) were significantly higher in group B than in group A, all with Ps < .05. We conclude that the retention of cumulus cells can improve the developmental competence of vitrified-thawed human mature oocytes and clinical pregnancy outcomes.

Objectives: To study pregnant outcomes of patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization and embryo transfer (IVF-ET), and analyze the differences of pregnant outcomes in patients with various phenotypes of PCOS., Methods: From Jan. 2005 to Feb. 2010, 631 PCOS patients (PCOS group) and 1423 patients with tubal infertility (control group) who underwent IVF-ET with matched age and body mass index were selected in Center for Reproductive Medicine of the Provincial Hospital Affiliated to Shandong University. Retrospective study was carried out, and pregnancy outcomes were compared between two groups., Results: The rates of abortion and preterm birth in PCOS group were significantly higher than those in control group [22.7% (143/631) vs. 18.69% (266/1423) and 11.2% (38/339) vs. 6.4% (51/794) respectively, all P < 0.05]. The rates of gestational diabetes mellitus were 1.5% (5/339) in PCOS and 0.6% (5/794) in control group, respectively; the rates of pregnancy induced hypertension syndrome were 4.7% (16/339) in PCOS and 3.0% (24/794) in control group; gestational days were (272 ± 13) days in PCOS and (273 ± 10) days in control group; the rates of neonatal deformity were 0.6% (2/339) in PCOS and 0.8% (6/794) in control group; weight of newborn infants in the two groups was (3.5 ± 0.5) kg; and there was no significant difference between two groups in the above index (all P > 0.05). Ovulatory PCOS patients had similar abortion rate [18.6% (19/102)] and preterm birth rate [8.2% (4/49)] when compared with those of control group (P > 0.05). Conversely, oligo-ovulatory PCOS patients showed higher abortion rate [23.4% (124/529)] and preterm birth rate [11.7% (34/290)] than those of control group (P < 0.05)., Conclusions: PCOS patients after IVF-ET have an increased abortion rate and preterm birth rate. However, ovulatory PCOS did not present various pregnancy complications. Non-polycystic ovary PCOS patients have worse pregnancy outcome. Ovarian dysfunction might be related to obstetric complications.

Objective: To explore the effects of sperm chromatin structure abnormalities on the outcome of in vitro fertilization and embryo transfer (IVF-ET)., Methods: Sperm DNA fragmentation and chromatin packaging defects were assessed in 136 couples undergoing IVF-ET because of infertility. The relationship between sperm DNA fragmentation, chromatin packaging defects and fertilization rate and clinical pregnancy was evaluated., Results: Both sperm DNA fragmentation and chromatin packaging defect had a negative correlation with fertilization rate (r=-0.198, P<0.05, and r=-0.389, P<0.01, respectively). Both parameters were higher in couples who failed to achieve pregnancy than those who achieved clinical pregnancy (10.74% vs. 5.40%, P<0.01 and 23.58% vs. 11.83%, P<0.01, respectively)., Conclusion: Abnormality of sperm chromatin structure is one of the reasons for IVF-ET failure. Examination of sperm chromatin structure is helpful in predicting the risk of IVF-ET failure and optimizing treatment of infertility.

Objective: To compare the effects of vitrification with slow-freezing on the developmental ability of day 3 cleavage stage embryos., Methods: Patients who had no less than 4 high quality embryos were included in this study. These embryos were cryopreserved using the methods of vitrification or slow-freezing. In the cryopreserved embryo transfer cycles, the embryos which were cryopreserved using one of the methods were chosen randomly. The developmental ability of embryos was compared between these two groups., Results: A total of 80 patients were included in this study with 160 embryos. In the group of slow-freezing, 73 (91%) embryos were survived and achieved 15 (38%) clinical pregnancies. Among these, 3 were twins and the implantation rate was 25% (18/73). In the group of vitrification, 71 (89%) embryos were survived and achieved 19 (48%) clinical pregnancies. Among these, 9 were twins and the implantation rate was 39% (28/71), which was significantly higher than the slow-freezing group (P < 0.05). Otherwise, the clinical pregnant rate and multiple pregnant rate was higher in the group of vitrification than the slow-freezing group, but had no significance., Conclusion: Vitrification is more benefit for the developmental ability of the thawed embryos and more suitable for the cryopreservation of day 3 cleavage stage embryos.

Objective: To assess the feasibility and clinical value of cryopreservation of human oocytes., Methods: Human oocytes were collected during stimulated cycle and then vitrificated with cryoloop. Surviving oocytes were thawed and then inseminated by intracytoplasmic sperm injection (ICSI). The fertilized oocytes were further cultured in vitro for 48 - 72 hours. High-quality embryos were transferred to the patients of infertility with informed consent., Results: A total of 235 oocytes were vitrificated and thawed. The survival and fertilization rates of the oocytes were 71.9% and 72.5% respectively. Forty-one embryos were transferred to 11 patients. Two of the 11 patients achieved pregnancy, one of which gave birth of 2 healthy female twin babies and the other was at the 16 th week of pregnancy. The mother and babies were all healthy., Conclusion: Human oocyte vitrification is safe and feasible.