Embryo Transfer Strategies for Women with Recurrent Implantation Failure During the Frozen-thawed Embryo Transfer Cycles:Sequential Embryo Transfer or Double-blastocyst Transfer?

Objective Both sequential embryo transfer(SeET)and double-blastocyst transfer(DBT)can serve as embryo transfer strategies for women with recurrent implantation failure(RIF).This study aims to compare the effects of SeET and DBT on pregnancy outcomes.Methods Totally,261 frozen-thawed embryo transfer cycles of 243 RIF women were included in this multicenter retrospective analysis.According to different embryo quality and transfer strategies,they were divided into four groups:group A,good-quality SeET(GQ-SeET,n=38 cycles);group B,poor-quality or mixed-quality SeET(PQ/MQ-SeET,n=31 cycles);group C,good-quality DBT(GQ-DBT,n=121 cycles);and group D,poor-quality or mixed-quality DBT(PQ/MQ-DBT,n=71 cycles).The main outcome,clinical pregnancy rate,was compared,and the generalized estimating equation(GEE)model was used to correct potential confounders that might impact pregnancy outcomes.Results GQ-DBT achieved a significantly higher clinical pregnancy rate(aOR 2.588,95%CI 1.267–5.284,P=0.009)and live birth rate(aOR 3.082,95%CI 1.482–6.412,P=0.003)than PQ/MQ-DBT.Similarly,the clinical pregnancy rate was significantly higher in GQ-SeET than in PQ/MQ-SeET(aOR 4.047,95%CI 1.218–13.450,P=0.023).The pregnancy outcomes of GQ-SeET were not significantly different from those of GQ-DBT,and the same results were found between PQ/MQ-SeET and PQ/MQ-DBT.Conclusion SeET relative to DBT did not seem to improve pregnancy outcomes for RIF patients if the embryo quality was comparable between the two groups.Better clinical pregnancy outcomes could be obtained by transferring good-quality embryos,no matter whether in SeET or DBT.Embryo quality plays a more important role in pregnancy outcomes for RIF patients.

Pregnancy Outcomes for Day 5 Versus Day 6 Single Frozen-thawed Blastocyst Transfer with Different Qualities of Embryos: A Large Matched-cohort Study

Objective This study aimed to determine whether the day of blastocyst expansion affects pregnancy outcomes in frozen-thawed blastocyst transfer(FBT)cycles.Methods A retrospective match-cohort study was conducted.Patients who underwent blastocyst transfer in frozen-thawed cycles at day 5 or 6 were matched for potential confounding factors.A total of 2207 matched pairs of FBT cycles were included from January 2016 to December 2019 in our Reproductive Medicine Center.Results The clinical pregnancy rate(CPR)and live birth rate(LBR)were significantly increased in day 5 blastocyst transfers when compared to day 6 blastocyst transfers,in terms of the same embryo quality.For FBT cycles with good-quality embryo,the CPR at day 5 and 6 was 61.30%and 57.56%,respectively(P=0.045),and the LBR was 44.79%and 36.16%,respectively(P<0.001).For FBT cycles with poor-quality embryo,the CPR at day 5 and 6 was 48.61%and 40.89%,respectively(P=0.006),and the LBR was 31.71%and 25.74%,respectively(P=0.019).The CPR for FBT cycles with good-quality embryo was statistically higher at day 6 than that at day 5 with poor-quality embryo transferred(57.56%vs.48.61%,P=0.001).Maternal age,anti-Müllerian hormone(AMH),endometrial thickness,embryo quality,and the day of blastocyst expansion were independently correlated with the CPR and LBR.The FBT cycles at day 5 had significantly higher CPR(adjusted odds ratio[OR]=1.246,95%confidence intervals[CI]:1.097–1.415,P=0.001)and LBR(adjusted OR=1.435,95%CI:1.258–1.637,P<0.001)than those at day 6.Conclusion The embryo quality is the primary indicator for FBT cycles.Day 5 blastocysts should be preferred when the quality of embryo at day 5 is the same as that at day 6.

Artificial Cycle with or without a Depot Gonadotropin-releasing Hormone Agonist for Frozen-thawed Embryo Transfer： An Assessment of Infertility Type that Is Most Suitable

The clinical outcomes of five groups of infertility patients receiving frozen- thawed, cleavage-stage embryo transfers with exogenous hormone protocols with or without a depot gonadotropin-releasing hormone （GnRH） agonist were assessed. A retrospective cohort analysis was performed on 1003 cycles undergoing frozen-thawed, cleavage-stage embryo transfers from January 1, 2012 to June 31, 2015 in the Reproductive Medicine Center of Wuhan General Hospital of Guangzhou Military Region. Based on the infertility etiologies of the patients, the 1003 cycles were divided into five groups： tubal infertility, polycystic ovary syndrome （PCOS）, endometriosis, male infertility, and unexplained infertility. The main outcome was the live birth rate. Two groups were set up based on the intervention： group A was given a GnRH agonist with exogenous estrogen and progesterone, and group B （control group） was given exogenous estrogen and progesterone only. The results showed that the baseline serum hormone levels and basic characteristics of the patients were not significantly different between groups A and B. The live birth rates in groups A and B were 41.67% and 29.29%, respectively （P〈0.05）. The live birth rates in patients with PCOS in groups A and B were 56.25% and 30.61%, respectively （P〈0.05）. The clinical pregnancy, implantation and on-going pregnancy rates showed the same trends as the live birth rates between groups A and B. The ectopic pregnancy rate was significantly lower in group A than in group B. We concluded that the live birth rate was higher and other clinical outcomes were more satisfactory with GnRH agonist co- treatment than without GnRH agonist co-treatment for frozen-thawed embryo transfer. The GnRH agonist combined with exogenous estrogen and progesterone worked for all types of infertility tested, especially for women with PCOS.

Live births from in vitro fertilization-embryo transfer following the administration of gonadotropin-releasing hormone agonist without gonadotropins:Two case reports

BACKGROUND The prevalence of female infertility between the ages of 25 and 44 is 3.5%to 16.7%in developed countries and 6.9%to 9.3%in developing countries.This means that infertility affects one in six couples and is recognized by the World Health Organization as the fifth most serious global disability.The International Committee for Monitoring Assisted Reproductive Technology reported that the global total of babies born as a result of assisted reproductive technology procedures and other advanced fertility treatments is more than 8 million.Advancements in controlled ovarian hyperstimulation procedures led to crucial accomplishments in human fertility treatments.The European Society for Human Reproduction and Embryology guideline on ovarian stimulation gave us valuable evidence-based recommendations to optimize ovarian stimulation in assisted reproductive technology.Conventional ovarian stimulation protocols for in vitro fertilization(IVF)–embryo transfer are based upon the administration of gonadotropins combined with gonadotropin-releasing hormone(GnRH)analogues,either GnRH agonists(GnRHa)or antagonists.The development of ovarian cysts requires the combination of GnRHa and gonadotropins for controlled ovarian hyperstimulation.However,in rare cases patients may develop an ovarian hyper response after administration of GnRHa alone.CASE SUMMARY Here,two case studies were conducted.In the first case,a 33-year-old female diagnosed with polycystic ovary syndrome presented for her first IVF cycle at our reproductive center.Fourteen days after triptorelin acetate was administrated(day 18 of her menstrual cycle),bilateral ovaries presented polycystic manifestations.The patient was given 5000 IU of human chorionic gonadotropin.Twenty-two oocytes were obtained,and eight embryos formed.Two blastospheres were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.In the second case,a 37-year-old woman presented to the reproductive center for her first donor IVF cycle.Fourteen days after GnRHa administration,the transvaginal ultrasound revealed six follicles measuring 17-26 mm in the bilateral ovaries.The patient was given 10000 IU of human chorionic gonadotropin.Three oocytes were obtained,and three embryos formed.Two high-grade embryos were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.CONCLUSION These two special cases provide valuable knowledge through our experience.We hypothesize that oocyte retrieval can be an alternative to cycle cancellation in these conditions.Considering the high progesterone level in most cases of this situation,we advocate freezing embryos after oocyte retrieval rather than fresh embryo transfer.

Kidding after Transfer of in Vitro Produced Saanen Goat Embryos into Local Ukrainian Breed Recipients in Different Seasons

In recent years, the demand for goat products has been growing due to the fact that goat milk has a number of advantages over cow milk, for example, it is low in lactose, and is considered less allergenic and easier to digest. To increase production during both breeding and non-breeding seasons and reduce the price of dairy products, it is necessary to effectively use reproductive management and assisted reproductive technologies. In vitro embryo production makes it possible to obtain a large number of eggs from goats, which for some reason are unable to conceive, but have genetic value. Afterward in vitro produced embryos can be transferred into recipient goats of other less genetically valuable breeds, such as the Ukrainian local breed. Therefore, the aim of the present study was to investigate the effectiveness of transfers of in vitro produced embryos of Saanen goats into surrogate sires of the Ukrainian local breed in different seasons. All manipulations with animals were carried out following ethical standards (Strasbourg, 1986). Six Saanen goats were selected as the oocyte donors. After the hormonal stimulation oocytes were retrieved by laparoscopic ovum pick-up. In vitro produced embryos were transferred laparotomically into 24 recipients of Ukrainian local breed. Fifty days after embryo transfers, pregnancies were determined by ultrasound diagnostics. Although the embryo development rate in the breeding season was 20% higher than in the non-breeding season, there was no difference in pregnancy and kidding rates between seasons. In conclusion, the transfer of in vitro produced Saanen goat embryos to recipients of the Ukrainian local breed gives the opportunity to achieve pregnancy and kidding regardless of the breeding season, which will enable a faster and more efficient increase in the livestock of highly productive goats in Ukraine in the post-war period.

Is the Mock Transfer Enough Reliable to Evaluate Hysterometry for Embryo Transfer?

Objectives: The aim of this study was to assess the reliability of the mock transfer during in vitro fertilization process Method: A case-control study was conducted on 134 patients included in IVF/ICSI cycles. From the hysterometry obtained during the mock transfer, the ideal embryo replacement site, i.e. two cm from the uterine fundus has been determined. Results: Significant differences were noted between the area estimated from the mock transfer and the area where the embryo was deposited during the actual embryo transfer. In fact, 15.9% of the patients had a difference between four and six cm, and 32% of the patients returning for a subsequent transfer had at least 2 cm of difference between the embryo deposit zones. This difference was significant (P 0.00) Conclusion: More than ultrasound guidance, the challenge with embryo transfer is to be able to minimize variations in the length of the uterus. This would make it possible to determine the ideal transfer depot area without multiple manipulations.

Pregnancy outcomes following supplementation of single dose GnRH agonist to sustain the luteal phase in antagonist fresh embryo transfer cycles:A multicentric prospective cohort study

Objective:To determine whether a single dose of gonadotropin-releasing hormone(GnRH)agonist administered subcutaneously in addition to the regular progesterone supplementation could provide a better luteal support in antagonist protocol fresh embryo transfer cycles.Methods:This prospective,multicentric,cohort study included total 140 women,70 in each group.Controlled ovarian stimulation was carried out as per fixed GnRH antagonist protocol.The trigger was given with hCG.In vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)was performed and day-3 embryos were transferred.Patients were divided into groups 1 and 2 based on computer generated randomization sheet.Six days following oocyte retrieval,group 1 received 0.2 mg decapeptyl subcutaneously in addition to regular progesterone support while group 2 received progesterone only.Luteal support was given for 14 days to both groups;if pregnancy was confirmed luteal support was continued till 12 weeks of gestation.The clinical pregnancy rate was the primary outcome.The implantation rate,miscarriage rate,live birth delivery rate,and multiple pregnancy rates were the secondary outcomes.Results:A total of 140 patients were analysed,70 in each group.Clinical pregnancy rates(47.1%vs.35.7%;P=0.17),implantation rates(23.4%vs.18.1%,P=0.24),live birth delivery rates(41.4%vs.27.1%,P=0.08),and multiple pregnancy rates(21.2%vs.16.0%,P=0.74)were higher in group 1 than in group 2.Group 1 had a lower miscarriage rate than group 2(5.7%vs.8.6%;P=0.75).However,these differences were not statistically significant between the two groups.Conclusions:Administration of a single dose of GnRH agonist in addition to regular natural micronized vaginal progesterone as luteal support in GnRH antagonist protocol cycles marginally improves implantation rates,clinical pregnancy rates,and live birth delivery rates.However,more studies with higher sample sizes are needed before any conclusive statements about GnRH agonist as luteal phase support can be made.

Effect of Mitochondrial Function of Ovarian Granulosa Cells on In Vitro Fertilization and Embryo Transfer Outcomes in Obese Polycystic Ovary Syndrome Patients

Objective:To investigate the effect of abnormal ovarian granulosa cell metabolism on in vitro fertilization and embryo transfer(IVF-ET)outcomes in obese polycystic ovary syndrome(PCOS)patients.Methods:Patients with PCOS who met the study criteria were screened according to the inclusion criteria.A total of 32 patients with obese PCOS were recruited into the study group,and 39 patients with non-obese PCOS were recruited into the control group.The general data(age,body mass index,and years of infertility),insulin resistance index(HOMA-IR),follicle-stimulating hormone(FSH),luteinizing hormone(LH),granulosa cell mitochondrial function,and IVF-ET outcome of patients in the study group and control group were retrospectively analyzed.Results:The differences in age and years of infertility between the study group and the control group were insignificant(P>0.05),and the body mass index(BMI)of the study group and control group was 30.5±1.24 kg/m2 and 22.3±1.12 kg/m2,respectively,in which the difference was statistically significant(P<0.05);the HOMA-IR of the study group was significantly higher than that of the control group(P<0.05);the reactive oxygen species(ROS)in the study group was significantly higher than that in the control group(P<0.05),and the ATP content in the study group was significantly lower than that in the control group(P<0.05);comparing the FSH and LH levels between the two groups,the difference was not statistically significant(P>0.05);the rate of IVF-ET failure was significantly higher in the study group than in the control group.Conclusion:PCOS is a complex endocrine disorder,and obesity is one of the independent risk factors for the development of PCOS.

Improvement of Live Birth Rate Following Frozen-Thawed Blastocyst Transfer by Combination of Prednisolone Administration and Stimulation of Endometrium Embryo Transfer

The endometrial condition is a significant factor for successful pregnancy. To regulate endometrial function in fertility treatment, prednisolone (PSL) is administered for suppression of increased natural killer cells and stimulation of endometrium embryo transfer (SEET) to enhance communication between embryo and maternal tissues. We attempted to improve the endometrial condition by PSL administration and SEET during frozen–thawed blastocyst transfer (FBT). Patients took PSL (5 mg) 3 times daily for 3 days after ovulation during the FBT cycle. To analyse effects of PSL combined with SEET, we determined rates of chemical pregnancy, clinical pregnancy, foetal heart movement (FHM) and live birth. Rates of chemical pregnancy, clinical pregnancy and FHM were significantly higher in the PSL(+)/SEET(+) (57.7%, 50.0% and 46.2%, respectively) and PSL(+)/SEET(-) (53.3%, 46.7% and 46.7%, respectively) groups than in the PSL(-)/SEET(+) (30.3%, 18.2% and 18.2%, respectively) and PSL(-)/SEET(-) (22.4%, 22.4% and 18.4%;P = 0.0043, 0.0081 and 0.0055, respectively) groups. The live birth rate was significantly higher in the PSL(+)/SEET(+) group than in the PSL(+)/SEET(-), PSL(-)/SEET(+) and PSL(-)/SEET(-) groups (42.3%, 26.7%, 18.2% and 12.2%, respectively;P = 0.0237). PSL combined with SEET may be a useful adjunct to assisted reproductive technology in women who repeatedly fail to conceive by infertility treatment.

Serum β-hCG level on day 7 of frozen-thawed embryo transfer: association with the clinical pregnancy outcomes in artificial cycles

Objective:The relationship between serum beta human chorionic gonadotropin(β-hCG)levels of patients(7 days after the transplantation of frozen-thawed embryos)and the pregnancy outcomes was investigated.Methods:This study was designed as a retrospective clinical trial of 366 women who underwent frozen-thawed embryo transfers(FETs)in artificial cycles.Patients were divided into three groups:clinical pregnancy group,biochemical pregnancy group,and non-pregnant group according to their pregnancy outcomes.Serumβ-hCG levels were tested on day 4,7,9,11 and 14 after FET.Results:In the clinical pregnancy group,the serumβ-hCG levels after 7-day post-transplantation were significantly elevated(16.20 IU/L vs.3.07 vs.0.1 IU/L;P<0.05)compared with the other two groups.Furthermore,it was found that Area Under Curve(AUC=0.96)was significant with cut-off value higher than 4.26 IU/L(sensitivity=92.3%,specificity=90.2%)to predict the clinical pregnancy outcomes in the receiver operating characteristic(ROC)analysis ofβ-hCG concentrations on day 7 of post-transplantation.Conclusion:Our results suggested that the elevated serumβ-hCG levels on day 7 of post-transplantation could predict the positive clinical pregnancy outcomes in artificial FET cycles.

Perinatal outcomes of frozen-thawed embryo transfer following blastocyst-stage embryo transfer compared to those of cleavage-stage embryo transfer:analysis of 9408 singleton newborns using propensity score analysis

Objective:Regarding frozen-thawed embryo transfer(FET),there is limited consensus on whether extending embryo culture from the cleavage stage to the blastocyst stage affects perinatal outcomes.This study aimed to compare perinatal outcomes of singletons between blastocyst-stage embryo transfer(BT)and cleavage-stage embryo transfer(CT)in FET.Methods:A total of 9408 FET cycles that met the inclusion criteria were included in this retrospective cohort study between 2019 and 2022.Blastocyst-stage embryo transfers were performed in the BT group,and cleavage-stage embryo transfers were performed in the CT group.Multivariate logistic regression analyses were performed,as well as propensity score matching(PSM)to adjust for confounders.Results:After PSM,a higher risk of pre-term birth(PTB;odds ratio[OR]:1.23,95%confidence interval[CI]:1.00-1.50,P=0.048)and being large for gestational age(LGA;OR:1.16,95%CI:1.00-1.35,P=0.050)was observed in the BT group compared to that in the CT group.After stratified PSM,in the subgroup under 35 years of age,only an increased risk of LGA was observed in the BT group compared to the CT group.Perinatal outcomes in the double-embryo transfer subgroup were similar to those in the unstratified group.However,in the subgroup beyond 35 years of age and the single embryo transfer subgroup,perinatal outcomes were not statistically different between the BT and CT groups(P>0.05).Conclusions:In FET,prolonged embryo culture to the blastocyst stage increased the risk of PTB and LGA in single fetuses.However,stratified analysis based on age and the number of transferred embryos yielded different results,necessitating further mechanistic studies.

Impact of gonadotropin-releasing hormone agonist and hormone replacement therapy on pregnancy outcomes in single euploid frozen-thawed embryo transfer for patients with endometrial polyps

Objective:Although consensus on the optimal endometrial preparation protocol for frozen-thawed embryo transfer(FET)is lacking,this is particularly true for patients with infertility and a history of endometrial polyps(EPs).In this study,we aimed to investigate whether a gonadotropin-releasing hormone agonist combined with hormone replacement therapy(GnRHa-HRT)could improve pregnancy outcomes in single euploid FET for patients with a history of EPs.Methods:In this retrospective cohort study,395 women who underwent their first single euploid FET cycle were divided into groups according to endometrial preparation protocols as follows:natural cycle(NC)(n=220),hormone replacement therapy(HRT)(n=122),and GnRHa-HRT groups(n=53).Subsequently,the FET cycles in the three groups were subdivided according to maternal age.All patients underwent hysteroscopic polypectomy before FET,and their EPs were confirmed by pathology.Results:No statistically significant differences were observed in live birth rates among the three groups(58.64%vs.58.20%vs.56.60%,P=0.964).Furthermore,the rates of miscarriage,ectopic pregnancy,premature live birth,and pregnancy complications were comparable among the three groups(P>0.05).After adjusting for potential confounding factors,no significant differences in pregnancy outcomes were reported between the groups(adjusted odds ratios[OR]and 95%credible intervals[CI]for live birth rate,HRTvs.NC:1.119,0.660–1.896,P=0.677;GnRHa-HRTvs.NC:1.165,0.610–2.226,P=0.643).Additionally,the pregnancy outcomes of the FET cycle were not influenced by the endometrial preparation protocols in the subgroups when stratified by maternal age(P>0.05).Conclusion:GnRHa-HRT did not improve the pregnancy outcomes of the single euploid FET in patients with a history of EPs.

Asynchronous Embryo Transfer in Sheep:Lack of Survival in Progestinized Recipient Ewes

Synchronization of development between the embryo and uterus is required for successful pregnancy establishment. Transfer of early embryos requires synchrony with the recipient uterus of 2 days or less in sheep, because asynchrony of 3 days or more results in failure of pregnancy recognition signaling for maintenance of corpus luteum （CL） and progesterone （P4） production and/or uterine support of the embryo. The objective was to determine if P4 treatment of recipient ewes would obviate the need for pregnancy recognition signaling and maintain a uterine environment conducive to embryo survival after asynchronous transfer, thereby establishing a universal recipient. Embryos （morulae/blastocysts） were recovered on day 6 from super-ovulated donor ewes. Recipient ewes received 25 mg P4 daily from day 6 post-estrus until 60 days after embryo transfer. Embryos were transferred into recipients on day 6,9, 12,18, or 30 post-estrus. The pregnancy rate on day 22 post-transfer was 60% for synchronous transfers to day 6 ewes, 44% and 22% for asynchronous transfers to day 9 and 12 ewes, and 0% for asynchronous transfers to day 18 and 30 ewes. On day 39 posttransfer ,pregnancy rates remained 60% for day 6 ewes,33% for day 9 ewes,and 0% for day 12,18, and 30 ewes. The P4 treatment did extend the window of uterine receptivity to early embryos in ewes by one day ,but did not create a universal recipient. Available results support the idea that a window of uterine receptivity to the conceptus exists in sheep that is independent of pregnancy recognition signaling.

Basal Serum Anti-Miillerian Hormone Level as a Predictor of Clinical Outcomes in Freezing-all Embryo Transfer Program

As a novel biomarker,there is inconsistent evidence regarding the association between anti-Miillerian hormone (AMH) and live birth rate in freezing-all embryo transfer cycles.We aim to assess the prognostic effect of baseline AMH on clinical outcomes,especially live birth rate in freezing-all embryo transfer cycles.A total of 828 non-polycystic ovary patients that underwent their first frozen-thawed embryo transfers in our center between January 2010 and January 2015 were recruited in this retrospective analysis.Patients were stratified into three groups based on their baseline AMH concentration:low AMH group (<1.4ng/mL),middle AMH group (1.4-5.8 ng/mL)and high AMH group (>5.8 ng/mL).The results showed that low AMH level was associated With adverse clinical outcomes.The differences in implantation rate (21.9% vs.43.2% vs.58.8%,P<0.001),clinical pregnancy rate (32.0% vs.55.2% vs.65.7%, P<0.001),live birth delivery rate (21.8% vs.43.6% vs.52.7%,P<0.001)and miscarriage rate (31.8% vs.17.5% vs.15.4%,P=0.014)among the three groups were statistically significant.After adjusting confounders (i.e.age,baseline FSH level,AFC,endometrium thickness,endometriurn preparation protocols,number of embryos transferred,etiologies of infertility),differences in live birth rate,clinical pregnancy rate and implantation rate between groups remained significant.The further age subgroup analysis demonstrated that low AMH concentration was significantly associated with poor outcomes both in young and advanced patients.The area under the curve for serum AMH,age,AFC and FSH were 0.635,0.634,0.615 and 0.543 respectively,for predicting live birth.In conclusion, baseline AMH was an independent prognostic factor of live birth rate of freezing-all embryo transfers,but its predictive value on live birth rate was of limited clinical value.

Untreated Prior Pulmonary Tuberculosis Adversely Affects Pregnancy Outcomes in Infertile Women Undergoing in vitro Fertilization and Embryo Transfer: A Large Retrospective Cohort Study

Objective Prior pulmonary tuberculosis(PTB) on chest X-ray(CXR) was commonly found in infertile patients receiving examinations before in vitro fertilization and embryo transfer(IVF-ET). It was unclear whether untreated PTB would affect pregnancy outcomes after IVF-ET.Method We conducted a retrospective cohort study of 14,254 infertile patients who had received IVFET at Peking University Third Hospital in 2017. Prior PTB was defined as the presence of signs suggestive of old or inactive PTB on CXR, with or without a clinical TB history. Patients who had prior PTB on CXR but had not received a clinical diagnosis and anti-TB therapy were included for analysis. Live birth,clinical pregnancy, and miscarriage rates were compared between the untreated PTB and non-PTB groups.Results The untreated PTB group had significantly lower clinical pregnancy(31.7% vs. 38.1%) and live birth(23.8% vs. 30.6%) rates than the non-PTB group(both P < 0.001). Multivariate analysis revealed that untreated PTB was a risk factor for decreased live birth rate [odds ratio(OR), 0.80;95% confidence interval(CI), 0.66–0.98;P = 0.028] in all patients and for increased miscarriage(OR, 4.19;95% CI,1.69–10.39;P = 0.002) and decreased live birth(OR, 0.45;95% CI, 0.24–0.83;P = 0.011) rates in patients with unexplained infertility.Conclusions Untreated PTB was associated with adverse pregnancy outcomes after IVF-ET, especially in patients with unexplained infertility, highlighting the clinical significance of PTB in this specific patient population.

Influence of Blastocysts Morphological Score on Pregnancy Outcomes in Frozen-thawed Blastocyst Transfers: a Retrospective Study of 741 Cycles

The influence of inner cell mass （ICM） and trophectoderm （TE） score on pregnancy out- comes in frozen-thawed blastocyst transfer cycles was analyzed. A retrospective analysis of 741 cycles of frozen-thawed blastosysts transfer was performed. All cycles were divided into four groups based on the number and morphological score of blastocysts： S-ICM B/TE B group （n=91）, the single blastocyst transfer oflCM B and TE B; D-ICM B/TE B group （n=579）, double blastocysts transfer oflCM B/TE B; D-1CM B/TE C group （n=35）, double blastocysts transfer of ICM B/TE C; and D-ICM C/TE B group （n=36）, double blastocysts transfer ofTE B/ICM C. The pregnancy outcomes were compared among the four groups. As compared with D-ICM B/TE C group, the clinical pregnancy rate, implantation rate and multiple pregnancy rate were increased in D-ICM B/TE B group （74.96% vs. 57.14%, 57.43% vs. 37.14%, and .48.62% vs. 25%, respectively, P〈0.05 for all）. Clinical pregnancy rate and implantation rate in D-ICM B/TE B group were also higher than in D-ICM C/TE B group （74.96% vs. 50%, and 57.43% vs. 33.33%, both P〈0.05）. Multivariable Logistic regression analysis indicated that ICM score was a better predictive parameter for clinical pregnancy （OR=3.05, CI 1.70-5.46, P〈0.001）, while the trophectoderm score was a better one for early abortion （OR=0.074, CI 0.03-0.19, P〈0.001）. Clinical pregnancy rate and multiple pregnancy rate in S-ICM B/TE B group were significantly lower than those in D-ICM B/TE B group （46.15% vs. 74.96%, and 2.38% vs. 48.62%, both P〈0.05）, but there was no si~,,niflcant difference in the implantation rate between the two groups. It was suggested that the higher score of ICM and TE may be indicative of the better pregnancy outcomes. The ICM score is a better predictor of clinical pregnancy than TE, while TE score is a better one in predicting early abortion. Sin- gle ICM B/TE B blastocyst transfer in frozen-thawed cycles can also get satisfactory pregnancy out- comes.

High-quality Cleavage Embryo versus Low-quality Blastocyst in Frozen-thawed Cycles:Comparison of Clinical Outcomes

This study compared the clinical outcomes of the frozen-thawed cycles of high-quality cleavage embryos with low-quality blastocysts to provide a reference for the choice of frozen-thawed embryo transfer schemes and to improve clinical pregnancy rates.A retrospective analysis was performed on the clinical data of patients undergoing frozen-thawed embryo transfer at the Reproductive Medicine Center of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from 2016 to 2017.In total,845 cases were divided into a high-quality cleavage embryo group(group A)and a low-quality blastocyst group(group B).Each group was further divided into subgroups based on the number of transplants.Group A was categorized into two subgroups comprising of 94 cases in subgroup Al(1 high-quality 8-cell group)and 201 cases in subgroup A2(2 high-quality 8-cell group).Group B was divided into four subgroups consisting of 73 cases in subgroup B I(D53BC group),65 cases in subgroup B2(D54BC group),110 cases in subgroup B3(D63BC group),and 282 cases in subgroup B4(D64BC group).The pregnancy outcomes and neonatal outcomes between the groups were compared.The clinical pregnancy rates(56.72%and 60.00%)and live birth rates(47.76%and 46.15%)in subgroups A2 and B2 showed no significant differences,but these rates were significantly higher in subgroups A2 and B2 than in the rest subgroups(P<0.05).The multiple birth rate(26.32%)in the subgroup A2 was significantly higher than that in the rest subgroups(P<0.05).There were no statistically significant differences in the abortion rates among all groups(P>0.05).In terms of neonatal outcomes,there were no statistically significant differences in the proportion of premature births,sex ratios,and birth defects among the low-weight and gigantic infants(P>0.05).Transplanting two high-quality cleavage embryos during the frozen-thawed embryo transfer cycles could significantly increase clinical pregnancy rates and live birth rates,but at the same time,it also increased the risks of multiple births and complications to mothers and infants.The D54BC subgroup had the most significant advantages among all groups(P<0.05).The rest low-quality blastocysts had clinical outcomes similar to the single high-quality cleavage embryo group.

Intramural pregnancy after in vitro fertilization and embryo transfer:A case report

BACKGROUND Intramural pregnancy is a rare type of ectopic pregnancy,which is diagnosed by transvaginal ultrasound and magnetic resonance imaging.Management strategies vary depending on the site of the pregnancy,the gestational age and the desire to maintain fertility.The incidence of intramural pregnancy in assisted reproductive technology is higher than that in natural pregnancy.CASE SUMMARY We present a case of intramural pregnancy after in vitro fertilization and elective single embryo transfer following salpingectomy.The patient was completely asymptomatic and her serumβ-human chorionic gonadotropin level increased from 290 m IU/m L to 1759 m IU/m L.Three-dimensional transvaginal ultrasound indicated a heterogeneous echogenic mass arising from the uterine fundus which was surrounded by myometrium and a slender and extremely hypoechoic area stretching to the uterine cavity which was thought to be a fistulous tract.Therefore,we considered a diagnosis of intramural pregnancy and laparoscopic surgery was conducted at 7 wk gestation.CONCLUSION Early diagnosis and treatment of intramural pregnancy is significant for maintaining fertility.

Effect of intrauterine perfusion of granular leukocyte-colony stimulating factor on the outcome of frozen embryo transfer

BACKGROUND Treatment of thin endometrium with granular leukocyte-colony stimulating factor(G-CSF)remains controversial.AIM To investigate the effect of G-CSF on the outcome of frozen embryo transfer in patients with thin endometrium.METHODS A retrospective propensity score matching(PSM)study was performed to assess patients administered frozen embryo transfer at the Reproductive Medicine Center of the Affiliated Drum Tower Hospital of Nanjing University Medical School,in 2012-2018.The patients were divided into G-CSF intrauterine perfusion(G-CSF)and non-G-CSF groups,and clinical pregnancy,implantation,ectopic pregnancy,and early abortion rates between the two groups were compared.RESULTS Before PSM,372 cycles were enrolled,including 242 and 130 cycles in the G-CSF and non-G-CSF groups,respectively.Age(34.23±5.76 vs 32.99±5.59 years;P=0.047)and the blastula/cleavage stage embryo ratio(0.68 vs 0.37;P=0.011)were significantly elevated in the G-CSF group compared with the non-G-CSF group;however,clinical pregnancy(46.28%vs 51.54%;P=0.371)and embryo implantation(35.21%vs 35.65%;P=0.910)rates were similar in both groups.After PSM by age and blastula/cleavage stage embryo ratio,244 cycles were included(122 cases each in the G-CSF and non-G-CSF groups).The clinical pregnancy(50.82%vs 48.36%;P=0.701)and embryo implantation(37.38%vs 34.11%;P=0.480)remained similar in both groups.CONCLUSION Intrauterine infusion of G-CSF does not improve the clinical outcome of frozen embryo transfer in patients with thin endometrium.

Post-salpingectomy interstitial heterotopic pregnancy after in vitro fertilization and embryo transfer:A case report

BACKGROUND Heterotopic pregnancy(HP)refers to the coexistence of ectopic pregnancy and intrauterine pregnancy.Salpingectomy is proposed as a pretreatment before in vitro fertilization and embryo transfer(IVF-ET)to reduce the risk of HP.HP after IVF-ET occurs in women who had already underwent bilateral salpingectomy,even though it is extremely rare.CASE SUMMARY A case of a 29-year-old woman with recurrent interstitial HP after IVF-ET following salpingectomy is presented.The main symptom was a sudden and worsening pelvic pain.Physical examinations revealed signs of peritoneal bleeding and irritation with stable vital signs.Transvaginal ultrasound showed a live intrauterine pregnancy and another live embryo with cardiac activity in the left cornu extending beyond the lateral edge of the uterus.Her hemoglobin concentration was 8.0 g/dL,and serum human chorionic gonadotropin value was 171116.9 mIU/mL.With the diagnosis of ruptured HP with internal bleeding,an emergency laparoscopic resection of left cornu was performed.The interstitial pregnancy was removed with caution to protect the intrauterine pregnancy.After the surgical treatment,the intrauterine pregnancy continued with no complications.A healthy baby was delivered by caesarean section at 39 wk.Outcomes of another three cases are further summarized.CONCLUSION Post-salpingectomy HP is a rare but challenging condition.Surgical treatment is preferred in the case with a viable intrauterine pregnancy.