Clomiphene Citrate or Medroxyprogesterone Acetate with Human Menopausal Gonadotropin in Poor Responders during In vitro Fertilization/Intracytoplasmic Sperm Injection Treatments Combined with Embryo Cryopreservation?

Objective:This study aimed to compare the efficacy of clomiphene citrate(CC)with human menopausal gonadotropin(hMG)and that of medroxyprogesterone acetate(MPA)with hMG in poor responders defined according to the Bologna criteria.Methods:The data of patients with poor ovarian response(POR)according to the Bologna criteria from September 2016 to November 2017 were retrospectively reviewed.All participants received either CC+hMG or the progesterone-primed ovarian stimulation protocol(PPOS)protocol.Results:A total of 340 patients and 563 in vitro fertilization cycles were analyzed in this study.The incidence of spontaneous luteinizing hormone(LH)surge and the mean LH level on trigger day were significantly lower in the PPOS group than in the CC+HMG group(0.04%vs.3.49%and 4.26±3.59 vs.9.38±6.92 mIU/mL,respectively,P<0.05);however,the incidence of premature ovulation was similar between the two groups.The number of viable embryos harvested was not statistically different between the two groups(1.7±1.1 vs.1.5±0.8,P=0.06).The mean dose and duration of hMG were significantly higher in the PPOS group than in the CC+hMG group(908.7±556.6 vs.177.9±214.5 IU and 6.0±3.4 vs.1.2±1.5 days,respectively,P<0.05).However,the number of oocytes retrieved,number of metaphase II oocytes,and fertilization rate were comparable between the two groups.Conclusions:The CC with low-dose gonadotropin strategy was superior to the MPA with hMG protocol for POR.

The Clinical Outcomes of In Vitro Fertilization/Intracytoplasmic Sperm Injection Treatments in 43 Women with a History of Gestational Trophoblastic Disease

Background:To analyze the clinical outcomes of in vitro fertilization(IVF)/intracytoplasmic sperm injection treatments in women with a history of gestational trophoblastic disease(GTD).Methods:This retrospective study included 43 patients with a history of GTD as the study group and 43 matched patients as the control group.The patients in the study group were divided into two groups according to the therapy received.Patients in Subgroup A(n=32)underwent uterine curettage treatment only.Patients in Subgroup B(n=11)underwent uterine curettage combined with chemotherapy.The characteristics of ovarian stimulation and outcomes of embryos and pregnancy were compared.Results:In the first cycle,there was a higher number of retrieved oocytes and normal fertilized oocytes in the control group than those in the study group(9.2 vs.6.2 and 6.0 vs.4.0,respectively;P<0.05);however,a similar mature oocyte rate(83.5%vs.85.0%),normal fertilization rate(84.5%vs.80.1%),number of good-quality embryos(1 vs.2),and viable embryos(2 vs.2)were found between the two groups(P>0.05).There was no difference in the outcomes between Subgroup A and Subgroup B.There was a significant difference in thickness of the endometrium between the control group and study group(10.9 mm vs.9.2 mm,respectively;P<0.05).The biochemical pregnancy rate and ongoing pregnancy rate in the control group were significantly higher than those in the study group(51.4%vs.31.7%and 37.8%vs.18.3%,respectively;P<0.05).In the study group,28(93.3%)patients had intrauterine adhesion(IUA)and 23(76.7%)patients used an intrauterine device(IUD),which were both significantly higher than those in control group(P<0.05).In addition,the rate of IUA in second-look hysteroscopy was lower than that in the first surgery in the study group(P<0.05).Conclusions:Patients with a history of GTD can present with a similar normal fertilization rate and number of viable embryos.However,patients with a history of GTD may have a thinner endometrium and lower ongoing pregnancy rate.Hysteroscopy before frozen embryo transfer and usage of an IUD can improve the occurrence of IUA.

A Modified Ultra-Long Downregulation Protocol Improves Pregnancy Outcomes in High Body Mass Index Patients Undergoing In vitro Fertilization/Intracytoplasmic Sperm Injection Treatment

Objective:Overweight and obesity are increasingly epidemic and negatively related to reproductive outcome.The aim of this study was to investigate the advantages of a modified ultra-long downregulation protocol on pregnancy outcomes of patients with high body mass index(BMI)undergoingin vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI),compared to the long protocol(LP).Methods:We retrospectively analyzed the clinical data of 3,920 infertile patients at the Reproductive and Genetic Hospital of Citic-Xiangya from January 2012 to December 2017 by propensity score matching(PSM).Patients were divided into two groups:modified ultra-LP(MULP)(n=1,960)and LP(n=1,960).Results:In the MULP group,live birth rate(52.65%vs.46.79%,P<0.001,odds ratio[OR]:1.784,95%confidence interval[CI]:1.563-2.036),clinical pregnancy rate(62.50%vs.57.91%,P=0.003,OR:1.211,95%CI:1.066-1.377),and implantation rate(53.24%vs.49.65%,P=0.004,OR:1.155,95%CI:1.048-1.272)were statistically significantly higher than those of the LP group.Moreover,the cycle cancellation rates(12.70%vs.15.15%,P=0.027,OR:0.815,95%CI:0.68-0.977),abortion rates(12%vs.14.8%,P=0.046,OR:0.785,95%CI:0.619-0.996),and ectopic pregnancy rates(1.06%vs.2.11%,P=0.04,OR:0.497,95%CI:0.252-0.98)were lower than those in the LP group.Conclusion:The modified ultra-long downregulation protocol improved the pregnancy outcomes in patients with high BMI undergoing IVF/ICSI treatment,providing a potential option for physicians when deciding an optimized ovary stimulation protocol for high BMI patients.

Minimal volume vitrification of epididymal spermatozoa results in successful in vitro fertilization and embryo development in mice

This study compared three cryopreservation protocols on sperm functions, IVF outcomes, and embryo development. Epididymal spermatozoa cryopreserved using slow-cooling （18% w/v raffinose, RS-C） were compared with spermatozoa vitrified using 0.25 M sucrose （SV） or 18% w/v raffinose （RV）. The motility, vitality, and DNA damage （TUNEL assay） of fresh control （FC） spermatozoa were compared with post-thawed or warmed RS-C, RV, and SV samples. Mouse oocytes （n = 267） were randomly assigned into three groups for insemination： RV （n = 102）, RS-C （n = 86）, and FC （n = 79）. The number and the proportion of two-cell embryos and blastocysts from each treatment were assessed. Sperm motility （P 〈 0.01） and vitality （P 〈 0.05） were significantly reduced after vitrification compared with slow-cooled spermatozoa. However, DNA fragmentation was significantly reduced in spermatozoa vitrified using sucrose （15 - 1.8% [SV] vs 26 - 2.8% [RV] and 27 - 1.2% [RS-C]; P 〈 0.01）. Although the number of two-cell embryos produced by RS-C, RV, and FC spermatozoa was not significantly different, the number of blastocysts produced from two-cell embryos using RV spermatozoa was significantly higher than FC spermatozoa （P = 0.0053）. This simple, small volume vitrification protocol and standard insemination method allows successful embryo production from small numbers of epididymal spermatozoa and may be applied clinically to circumvent the need for ICSI, which has the disadvantage of bypassing sperm selection.

Effects of Endometrial Stimulation Timings and Techniques on Pregnancy Outcomes in Patients without Prior Embryo Transfer: A Systematic Review and Meta-Analysis

Objective:To investigate the effects of endometrial stimulation timings and techniques on pregnancy outcomes in patients without prior embryo transfer(ET).Methods:We included a total of 10 studies related to the impact of endometrial stimulation on the pregnancy outcome of infertile patients with the first ET from 2010 to 2019.These studies were found by searching databases including China Science and Technology Journal Database(VIP),Chinese Biological Med(CBM),Chinese Medical Current Content(CMCC),China National Knowledge Internet(CNKI),WanFang Med Online,Cochrane Library,Web of Science,PubMed,Medline,ScienceDirect,and EMBASE.A total of 1,983 cycles were included,of which 725 were cycles with endometrial stimulation.Clinical outcomes included clinical pregnancy,implantation,abortion,multiple pregnancy,and live birth rate.Results:The implantation rate(IR)was higher in the fresh cycle endometrial stimulation group than in the control group(relative risk[RR]=1.21,95%confidence interval[CI]=1.03-1.42;P=0.02),but there were no significant between-group differences in the live birth rate(LBR)and abortion rate(AR).Subgroup analysis showed that whether follicular or luteal endometrial stimulation was performed before the ET cycle had no effect on the clinical pregnancy outcome,and endometrial stimulation on the day of oocyte retrieval reduced the clinical pregnancy rate(CPR)(RR=0.37,95%CI=0.19-0.75;P=0.005).Whether the technique involved the use of a curette or catheter,there was no significant between-group difference in CPR.Conclusions:Fresh cycle endometrial stimulation can improve the embryo IR in patients without prior ET,but it cannot increase CPR,LBR,or AR.Subgroup analysis showed that different endometrial stimulation timings and techniques did not significantly improve CPR and that endometrial stimulation on the day of oocyte retrieval reduced CPR.

Development and Validation of a Nomogram for Predicting the Probability of Live Birth in Infertile Women

Objective:To develop a nomogram to predict the probability of live birth on the basis of the association of patient characteristics in subfertile individuals or couples.Methods:A retrospective study was conducted from January 2014 to December 2015.A nomogram was built from a training cohort and tested on an independent validation cohort.A total of 2,257 patients who had undergone their first nondonor cycle of in vitro fertilization(IVF)(including intracytoplasmic sperm injection)were randomly split 2:1 into training(n=1,527)and validation(n=730)cohorts.Results:There were no statistically significant differences in the patients’baseline and cycle characteristics between the training and validation cohorts.On multiple logistic regression analysis,female age,antral follicle count,tubal factor,anovulation,ethnicity,unexplained fertility,and male factor were significantly associated with live birth.The nomogram had a C-index of 0.700(95%confidence interval[CI]:0.698-0.701)in the training cohort and 0.684(95%CI:0.681-0.687)in the validation cohort.Conclusions:Our nomogram can predict the probability of live birth for infertile women and can be used to guide clinicians and couples to decide on an IVF treatment option.

Establishing the lower limits of total serum testosterone among Chinese proven fertile men who received treatment of assisted reproductive technology

Testosterone(T)plays a crucial role in spermatogenesis because extremely low levels of intratesticular T lead to correspondingly low serum levels of total T(tT),severe disorders of spermatogenesis,and male sterility.However,there is little consensus on the lower limits of serum tT in proven fertile men undergoing assisted reproductive technology treatments in Chinese or other Asian populations.We aimed to establish the reference range of serum tT based on a population of 868 fertile Chinese men undergoing in vitro fertilization or intracytoplasmic sperm injection and embryo transfer(IVF/ICSI-ET)treatments.We defined a fertile man as having had a live baby with his partner as recorded in our IVF registration system.The lower limits of serum tT were established using a Siemens IMMULITE 2000 chemiluminescent system.The 1st,2.5th,and 5th percentiles and their 95%confidence intervals(CIs)were 3.6(95%CI:2.7–4.1)nmol l−1,4.3(95%CI:4.1–5.0)nmol l−1,and 5.6(95%CI:4.8–5.8)nmol l−1,respectively.Using the linear correlation of serum tT between the Siemens platform and a liquid chromatography–tandem mass spectrometry platform,the calculated lower limits of serum tT were also established for fertile Chinese men undergoing IVF/ICSI-ET treatments,which will benefit the clinical diagnosis and treatment of male infertility during such procedures.