Sperm Injection Treatment Research Articles

Deficiency of primate-specific SSX1 induced asthenoteratozoospermia in infertile men and cynomolgus monkey and tree shrew models

Primate-specific genes (PSGs) tend to be expressed in the brain and testis. This phenomenon is consistent with brain evolution in primates but is seemingly contradictory to the similarity of spermatogenesis among mammals. Here, using whole-exome sequencing, we identified deleterious variants of X-linked SSX1 in six unrelated men with asthenoteratozoospermia. SSX1 is a PSG expressed predominantly in the testis, and the SSX family evolutionarily expanded independently in rodents and primates. As the mouse model could not be used for studying SSX1, we used a non-human primate model and tree shrews, which are phylogenetically similar to primates, to knock down (KD) Ssx1 expression in the testes. Consistent with the phenotype observed in humans, both Ssx1-KD models exhibited a reduced sperm motility and abnormal sperm morphology. Further, RNA sequencing indicated that Ssx1 deficiency influenced multiple biological processes during spermatogenesis. Collectively, our experimental observations in humans and cynomolgus monkey and tree shrew models highlight the crucial role of SSX1 in spermatogenesis. Notably, three of the five couples who underwent intra-cytoplasmic sperm injection treatment achieved a successful pregnancy. This study provides important guidance for genetic counseling and clinical diagnosis and, significantly, describes the approaches for elucidating the functions of testis-enriched PSGs in spermatogenesis.

The Influence of Vaginal Dysbiosis on Intracytoplasmic Sperm Injection Outcome.

In women of reproductive age, vaginal infection is a gynaecological condition with various health consequences. Bacterial vaginosis, vulvovaginal candidiasis, and aerobic vaginitis are the most prevalent types of infection. Although reproductive tract infections are known to impact human fertility, no consensus guidelines on microbial control in infertile couples undergoing in vitro fertilization therapy are currently available. This study aimed to determine the effect of asymptomatic vaginal infections on the outcome of intracytoplasmic sperm injection in infertile Iraqi couples. Forty-six asymptomatic infertile Iraqi women were evaluated for genital tract infections by taking a vaginal sample on ovum pick-up for microbiological culture during their intracytoplasmic sperm injection treatment cycle. Based on the acquired results, a multi-microbial community colonized the participant's female lower reproductive tract, and only 13 women achieved pregnancy compared to 33 who did not. Candida albicans was found in 43.5% of the cases, 39.1% Streptococcus agalactiae, 19.6% Enterobacter species, 13.0% Lactobacillus, 8.7% Escherichia coli, 8.7% Staphylococcus aureus, 4.3% Klebsiella, and 2.2% Neisseria gonorrhoeae. However, no statistically significant effect was observed on the pregnancy rate except for Enterobacter spp. and Lactobacilli. In conclusion, the majority of patients had a genital tract infection; Enterobacter spp. had a substantial negative influence on the pregnancy rate, and lactobacilli were highly related to positive outcomes in participating females.

A comprehensive analysis of chromosomal polymorphic variants on reproductive outcomes after intracytoplasmic sperm injection treatment

Recent studies suggest that chromosomal polymorphic variations are associated with infertility. A systematic review of chromosomal polymorphisms in assisted reproduction found an association with higher rates of miscarriage. Aim of this study is to analyse the influence of specific types or number of chromosomal polymorphic variations on reproductive outcomes of couples undergoing ICSI treatment. We analysed data from 929 fresh and frozen embryo transfer cycles of 692 women who underwent karyotyping analysis using Giemsa-Trypsin-Leishman (GTL) banding prior to the ICSI procedure at the Fertility Centre of Lanka Hospitals Corporation Plc, Sri Lanka, from January 2016 to December 2018. The outcomes of interest were the pregnancy, miscarriage and live birth rate per cycle. There was no evidence of a difference in the reproductive outcomes between carriers or non-carriers of any type or number of chromosomal polymorphic variation. Our data, in contrast to previous studies, does not support a deleterious effect for the type or number of chromosomal polymorphic variations on reproductive outcomes. However, additional prospective, adequately powered studies, conducted in multiethnic populations, are required to further investigate whether the detection of chromosomal polymorphic variants prior to assisted conception may in fact be a futile diagnostic tool.

Novel variants in ZP1, ZP2 and ZP3 associated with empty follicle syndrome and abnormal zona pellucida

Research questionWhich genetic variants might explain the causes of empty follicle syndrome (EFS) and abnormal zona pellucida (ZP) and affect the success of treatment with assisted reproductive technologies (ART)? DesignWhole-exome sequencing was performed in probands with EFS and abnormal ZP. Sanger sequencing was used for variant validation. Using HEK-293T cells, the effects of ZP1 and ZP2 variants on protein expression were explored by western blotting, and the effect of the ZP1 variant on protein location was investigated via immunofluorescence. The protein structure was also analysed to investigate the pathogenicity of variants. ResultsA homozygous nonsense variant in ZP1 (c.874C>T, p.Gln292*) was detected in a patient with EFS. A novel homozygous frameshift variant in ZP2 (c.836_837delAG, p.Glu279Valfs*6) and a novel heterozygous missense variant in ZP3 (c.1159G>A, p.Val387Met) were identified in two patients with ZP morphological abnormalities, respectively. Western blotting and immunofluorescence analysis showed that the ZP1 variant results in a premature stop codon, leading to the truncated ZP1 protein. The ZP2 variant, which is situated in the N-terminus, triggers the degradation of a premature termination protein. Additionally, the patient with the ZP3 variant achieved clinical pregnancy following intracytoplasmic sperm injection treatment. ConclusionsThese findings expand the mutational spectrum of ZP1, ZP2 and ZP3, and provide new evidence for genetic diagnosis of female infertility. The targeted genetic diagnosis of ZP genes is recommended to choose appropriate fertilization methods and improve success rates of treatment with ART.

Homozygous mutation in DNALI1 leads to asthenoteratozoospermia by affecting the inner dynein arms.

Asthenozoospermia is the most common cause of male infertility. Dynein protein arms play a crucial role in the motility of sperm flagella and defects in these proteins generally impair the axoneme structure and affect sperm flagella function. In this study, we performed whole exome sequencing for a cohort of 126 infertile patients with asthenozoospermia and identified homozygous DNALI1 mutation in one patient from a consanguineous family. This identified homozygous mutation was verified by Sanger sequencing. In silico analysis showed that this homozygous mutation is very rare, highly pathogenic, and very conserved. Sperm routine analysis confirmed that the motility of the spermatozoa from the patient significantly decreased. Further sperm morphology analysis showed that the spermatozoa from the patient exhibited multiple flagella morphological defects and a specific loss in the inner dynein arms. Fortunately, the patient was able to have his child via intracytoplasmic sperm injection treatment. Our study is the first to demonstrate that homozygous DNALI1 mutation may impair the integration of axoneme structure, affect sperm motility and cause asthenoteratozoospermia in human beings.

The serum oestradiol/progesterone ratio on the day of OPU + 7, but not the day of OPU + 5, affects the rates of live birth in fresh blastocyst embryo transfer cycles

BackgroundIn an in vitro fertilization (IVF) cycle, the embryo ends its wandering time and begins the process of implantation into the uterine cavity on the seventh day after oocyte pick-up (OPU + 7), which is closer than OPU + 5 to the time of nidation. Therefore, measuring the oestradiol (E2)/progesterone (P) ratio on OPU + 7 may be helpful for predicting pregnancy outcomes.MethodsThis is a retrospective cohort study of 2,257 women undergoing a follicular-phase depot gonadotropin-releasing hormone agonist (GnRH-a) protocol for in vitro fertilization /intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh blastocyst embryo transfer cycles at a university-affiliated fertility center between January 2016 and April 2021. First, 2,257 women were split into two groups based on clinical pregnancy for analyzing the levels of E2 and P and the E2/P ratio on the day of OPU + 2, OPU + 5 and OPU + 7. And then 2,257 cycles were stratified into three groups based on E2/P ratio tertiles on OPU + 7: the low group (1.3–15.7 pg/ng), middle group (15.7–28.8 pg/ng), and high group (28.8–487.2 pg/ng). The threshold effect of the E2/P ratio on OPU + 7 on live birth was investigated using a two-piecewise linear regression model and a smoothing function curve.ResultsThe level of P in the clinical pregnancy group were lower than that in the nonclinical pregnancy group on both OPU + 2 and OPU + 7 (201.9 ± 71.6 ng/ml vs 213.1 ± 77.6 ng/ml, 89.5 ± 88.5 ng/ml vs 99.5 ± 94.9 ng/ml, P < 0.05). The E2/P ratio in the clinical pregnancy group were higher than that in the nonclinical pregnancy group on both OPU + 2 and OPU + 7 (8.4 ± 6.5 pg/ng vs 8.0 ± 6.8 pg/ng, 32.3 ± 38.5 pg/ng vs 25.2 ± 31.0 pg/ng, P < 0.01). The E2/P ratio on OPU + 7 was positively associated with positive hCG (adjusted OR = 1.01; 95% CI, 1.01–1.02; P < 0.0001), clinical pregnancy (adjusted OR = 1.01; 95% CI, 1.00–1.01; P = 0.0067) and live birth (adjusted OR = 1.01; 95% CI, 1.00–1.01; P < 0.001), and a nonlinear correlation was observed between the E2/P ratio and LBR on OPU + 7.ConclusionsA higher E2/P ratio is associated with a higher LBR, but the E2/P ratio should be maintained within a suitable range.

Association of paternal MTHFR polymorphisms (C677T) with clinical outcomes in ICSI treatment.

This study aims to investigate the association between paternal methylenetetrahydrofolate reductase (MTHFR) polymorphisms (C677T) and embryonic development, pregnancy, and neonatal outcomes in intracytoplasmic sperm injection (ICSI) treatment. A total of 191 infertile men undergoing ICSI treatment at the Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, were recruited between January 2020 and June 2021. The MTHFR C677T polymorphism genotyping was evaluated in these male patients, and they were stratified into three groups according to genotyping results: Control (CC), heterozygote mutated (CT), and mutated homozygote (TT). In addition, we conducted a comparative analysis of embryonic development, pregnancy, and neonatal outcomes among these three groups. The embryonic development (including normal fertilization rate (80.14% vs. 83.06% vs. 85.10%; p = 0.37), high-quality embryo rate (45.26% vs. 43.69% vs. 46.04%; p = 0.72), blastocyst formation rate (42.47% vs. 43.18% vs. 39.38%; p = 0.62), implantation rate (42.47% vs. 36.25% vs. 41.22%; p = 0.62), and clinical pregnancy rate (64.71% vs. 58.75% vs. 66.67%; p = 0.59) were not comparable among these three groups. Moreover, no significant difference was observed in terms of pregnancy outcomes (including miscarriage rate (24.24% vs. 12.77% vs. 22.5%; p = 0.35) and live birth rate (49.02% vs. 51.25% vs. 51.66%; p = 0.96)). Additionally, no marked difference was observed in terms of neonatal outcome (including, preterm delivery rate (24% vs. 14.63% vs. 9.67%; p = 0.35), birth height (p = 0.75), birth weight (p = 0.35), neonatal sex (p = 0.48), gestational age at delivery (p = 0.24), Apgar score (p = 0.34), and birth defects (0% vs. 2% vs. 9%; p = 0.23) among the study groups. The paternal MTHFR C677T polymorphism is not associated with embryo quality, pregnancy, or neonatal outcomes in ICSI treatment. Therefore, in our population, MTHFR polymorphisms do not provide helpful information in explaining ICSI failure.

Slightly Elevated Progesterone on HCG Trigger Day Has an Impact on Pregnancy Outcomes of Fresh Single Blastocyst Transfer Cycles Under an Early Follicular Phase Prolonged Protocol Cycle.

The effect of premature progesterone elevation on assisted reproductive technology has been debated. In different ovarian stimulation protocols, ovarian responses, and embryos transferred, conflicting results reside regarding the impact of elevated progesterone on pregnancy outcomes, according to previous studies. In addition, most studies have focused on significantly elevated progesterone levels, eg, above 1.5ng/mL, 1.75ng/mL, 2ng/mL. However, studies focusing on levels that are just slightly elevated are lacking, and some have concluded that such levels have no adverse effects on pregnancy outcomes. Clinical data of patients who underwent early follicular phase prolonged protocol cycle in vitro fertilization/intracytoplasmic sperm injection treatment were collected. Patients were divided into two groups according to progesterone level on the trigger day of human chorionic gonadotropin (HCG): Group 1: <1.0ng/mL and Group 2: 1.0-1.5ng/mL. Differences in baseline characteristics, ovulation promotion, and embryo culture, along with clinical pregnancy outcomes, were compared between the two cohorts. A total of 743 participants were included in this study, of which 587 were included in Group 1 and 156 were included in Group 2. In terms of pregnancy outcomes, Group 2 had a significantly lower clinical pregnancy rate and live birth rate per cycle than Group 1 (64.1% vs 75.7%, p <0.05; 63.5% vs 72.7%, p <0.05). After correction for maternal age, maternal body mass index, infertility duration, basal follicle-stimulating hormone, anti-Müllerian hormone, antral follicle count, total dose of gonadotropin, days of stimulation, and estradiol level on HCG trigger day, slightly elevated progesterone levels (P>1.0ng/mL) remained a risk factor for pregnancy failure in fresh single D5 blastocyst transfer under an early follicular phase prolonged protocol cycle. Slightly elevated progesterone levels on HCG trigger day may negatively affect pregnancy outcomes in early follicular phase prolonged protocol cycles.

Estradiol pretreatment in GnRH antagonist protocol for IVF/ICSI treatment.

We conducted a systematic review and meta-analysis of all published data to determine the impact of estradiol pretreatment on reproductive outcomes and ovary stimulation characteristics for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment with gonadotropin-releasing hormone (GnRH) antagonist protocol. MEDLINE, EMBASE, Cochrane Library, Web of Science, and China National Knowledge Infrastructure were searched, and any randomized controlled trials associated with estradiol pretreatment in GnRH antagonist protocol were included. Seven studies (1,236 patients) were included in the present study. The pooled data from the meta-analysis demonstrated no significant difference in ongoing pregnancy rate (odds ratio (OR): 0.92 (95% CI: 0.69-1.21; P = 0.53) and live birth rate OR: 0.98 (95% CI: 0.74-1.30; P = 0.90) between patients with and those without estradiol pretreatment in GnRH antagonist protocol. Duration of gonadotropin exposure, gonadotropin consumption, and the number of cumulus-oocyte complexes were not significantly different between groups. Luteal estradiol pretreatment in IVF/ICSI cycles with GnRH antagonist protocol in normal ovary responding population does not affect the reproductive outcomes. It is an encouraging option to facilitate cycle scheduling in GnRH antagonist protocol, for luteal estradiol pretreatment does not increase the duration of gonadotropin exposure or gonadotropin consumption.

Impact of elevated body mass index on cumulative live birth rate and obstetric safety in women undergoing assisted reproductive technology

This study evaluated the impact of elevated body mass index (BMI) on short- and long-term outcomes of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments. A total of 7229 patients undergoing IVF/ICSI fresh cycles and subsequent frozen embryo transfer cycles from 2014 to 2020 were divided into normal (18.5–24.9 kg/m2) and high BMI (≥ 25 kg/m2) groups. Ovarian response, pregnancy outcomes, and safety of both mother and fetus were the main outcome measures. Furthermore, multivariate analysis was used to determine whether BMI was associated with cumulative live birth rate (CLBR). Results showed that for younger women (< 38 year), CLBR was significantly reduced in the high BMI group compared with the normal BMI control and was accompanied by fewer retrieved oocytes and available embryos. Additionally, the incidence of hypertensive disorders of pregnancy, fetal macrosomia, and cleft lip and palate birth defects resulting from cumulative live births was significantly higher compared with the normal BMI group. No differences were observed among older women (≥ 38 year). Multivariate analysis revealed that high BMI was a risk factor for CLBR. Our study suggested that elevated BMI has a greater adverse impact on younger women.

Associations of maternal obesity, frozen embryos, and offspring adverse cardiometabolic alterations

To evaluate the long-term cardiometabolic health of offspring conceived by frozen embryo transfer and born to mothers with overweight/obesity. Retrospective cohort study. Center for Reproductive Medicine. A total of 2,741 offspring born to mothers who underwent invitro fertilization/intracytoplasmic sperm injection treatment were followed between June 2014 and August 2021. The offspring were singletons aged 4-11 years at follow-up. None. Age-specific z-scores of cardiometabolic parameters were examined, including adiposity, systolic/diastolic blood pressure, glucose, and lipid profiles, and the metabolic sum score of different cardiometabolic characteristics. Of 2,741 offsprings, 965 (35.21%) were born to mothers with overweight/obesity, including 396 (41.04%) offspring who were conceived by frozen embryo transfer. After adjusting for paternal and maternal age, paternal body mass index (BMI), offspring age, offspring sex, and offspring postnatal energy intake, offspring born to mothers with overweight/obesity and conceived by frozen embryo transfer showed a significantly higher BMI z-score, systolic blood pressure z-score, metabolic sum score-1, and metabolic sum score-2 compared with those conceived by fresh embryo transfer (BMI z-score: adjusted mean difference, 0.17; 95% confidence interval [CI], 0.04-0.30; systolic blood pressure z-score: adjusted mean difference, 0.16; 95% CI, 0.02-0.29; metabolic sum score-1: adjusted mean difference, 0.54; 95% CI, 0.15-0.94; metabolic sum score-2: adjusted mean difference, 0.45; 95% CI, 0.07-0.83). However, in offspring of mothers with normal weight, offspring conceived by frozen embryo transfer showed a significantly lower low-density lipoprotein-cholesterol z-score compared with those conceived by fresh embryo transfer (adjusted mean difference, -0.12; 95% CI, -0.22 to -0.02). Other cardiometabolic parameters were comparable between offspring with frozen and fresh embryo transfers after adjusting for multivariate confounder variables. This study found that among offspring from mothers who were overweight/obese, those offspring conceived by frozen embryo transfer were associated with higher systolic blood pressure z-scores and adverse metabolic changes compared with those conceived by fresh embryo transfer. The changes show that the association between frozen embryo transfer and offspring adverse cardiometabolic changes is apparent only among those born to mothers who are overweight/obese.

Comparing the effects of endometrial injury in the luteal phase and follicular phase on in vitro fertilization treatment outcomes.

Several studies have shown that endometrial injury improves clinical pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment with a history of implantation failure. However, endometrial injury can be performed in the follicular phase (FP) followed by embryo transfer in the same menstrual cycle or in the luteal phase (LP) before the embryo transfer cycle. This prospective cohort study was conducted from January 2015 to September 2021, and a total of 487 patients were included. All included patients had a history of a failed implantation cycle. They were divided into two groups: the FP group (N = 330), in which endometrial injury was performed on menstrual day 3-5, and the LP group (N = 157), in which endometrial injury was performed in the cycle preceding embryo transfer 7 days after ovulation. First, in unselected patients, the implantation rate and clinical pregnancy rate were comparable between the LP and FP groups. However, in patients with a history of ≥ 2 failed transfer cycles, the implantation rate was significantly higher in the LP group than in FP group (43.09% versus 33.33%, P = 0.03). Moreover, the clinical pregnancy rate was also significantly higher in patients in the LP group than in patients in the FP group (60.17% versus 46.15%, P=0.02). In addition, logistic regression analysis showed that endometrial injury in the LP group was an independent factor affecting clinical pregnancy outcome in patients with a history of ≥ 2 failed transfer cycles (aOR = 2.05, 90% CI:1.22-3.47, P=0.01). Endometrial injury improves pregnancy outcomes when performed in the luteal phase compared with the follicular phase in patients with a history of ≥ 2 failed transfer cycles but not in unselected patients.

Effects of microvibration stimulation on developmental potential of discarded germinal vesicle oocytes of human.

This research aims to study the effects of continuous microvibration stimulation on the parthenogenetic development of human germinal vesicle oocytes. Ninety-five discarded germinal vesicle oocytes from intracytoplasmic sperm injection treatment (ICSI) cycles performed at Amcare Women's & Children's Hospital between January and December 2021 were used for conventional static culture as well as 10Hz microvibration culture. We investigated the differences between the two groups in terms of oocyte maturation rate, parthenogenetic activation rate, and parthenogenetic blastocyst formation rate. The static culture and 10Hz microvibration culture of 95 oocytes showed that the parthenogenetic blastocyst formation rate in the microvibration culture group was significantly higher than those in the traditional static culture group. A continuous microvibration stimulation can significantly improve the parthenogenetic developmental potential of human immature oocytes.

Loss-of-function mutations in CEP78 cause male infertility in humans and mice.

Centrosomal protein dysfunction might cause ciliopathies. However, the role of centrosomal proteins in male infertility remains poorly defined. Here, we identified a pathogenic splicing mutation in CEP78 in male infertile patients with severely reduced sperm number and motility, and the typical multiple morphological abnormalities of the sperm flagella phenotype. We further created Cep78 knockout mice, which showed an extremely low sperm count, completely aberrant sperm morphology, and approximately null sperm motility. The infertility of the patients and knockout mice could not be rescued by an intracytoplasmic sperm injection treatment. Mechanistically, CEP78 might regulate USP16 expression, which further stabilizes Tektin levels via the ubiquitination pathway. Cep78 knockout mice also exhibited impairments in retina and outer hair cells of the cochlea. Collectively, our findings identified nonfunctional CEP78 as an indispensable factor contributing to male infertility and revealed a role for this gene in regulating retinal and outer hair cell function in mice.

Does hysteroscopic resection of polyps require cycle cancellation in women undergoing controlled ovarian hyperstimulation in the ICSI cycle?

Objective:Endometrial polyps are one of the most extensive pathologies in the uterus and can be detected incidentally during assisted reproductive therapy in asymptomatic women.Materials and Methods:In patients planned for in vitro fertilization or intracytoplasmic sperm injection (ICSI) treatment, embryo freezing, or cycle cancelation options are mandatory in many clinics when detected at the beginning of the cycle. In our study, in ICSI treatment, patients with a single endometrial polyp smaller than 1.5 cm, who underwent hysteroscopic polyp resection at the beginning of the cycle and underwent fresh embryo transfer without canceling the treatment (n=31), and patients with the same characteristics of endometrial polyp who underwent hysteroscopic polyp resection before the cycle (n=34) are compared within the pregnancy, abortion and live birth rates.Results:As a result, no statistical difference was found between the two groups’ pregnancy, abortion, and live birth rates.Conclusion:Hysteroscopic resection of polyps during ovarian stimulation in ICSI treatment does not affect pregnancy and live birth rates and may eliminate the necessity of freezing.

The impact of different endometrial preparation protocols on obstetric and neonatal complications in frozen-thawed embryo transfer: a retrospective cohort study of 3,458 singleton deliveries

BackgroundFrozen-thawed embryo transfer (FET) is thought to be associated with obstetric and neonatal complications after in vitro fertilization/intracytoplasmic single sperm injection (IVF/ICSI) treatment. The study aimed to determine whether the endometrial preparation protocol is an influencing factor for these complications.MethodsWe conducted a retrospective cohort study of 3,458 women who had singleton deliveries after IVF/ICSI–FET treatment at the Centre for Reproductive Medicine of Shanghai First Maternity and Infant Hospital between July 2016 and April 2021. The women were divided into three groups according to the endometrial preparation protocols: 2,029 women with programmed cycles, 959 with natural cycles, and 470 with minimal ovarian stimulation cycles. The primary outcomes were the incidence rates of obstetric and neonatal complications, namely, hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP), placenta previa, preterm rupture of membranes (PROM), preterm delivery, postpartum haemorrhage, large for gestational age (LGA), small for gestational age (SGA), and macrosomia.ResultsAfter adjustments for confounding variables by multivariate logistic regression analysis, the results showed that programmed cycles had an increased risk of HDP (aOR = 1.743; 95% CI, 1.110–2.735; P = 0.016) and LGA (aOR = 1.269; 95% CI, 1.011–1.592; P = 0.040) compared with natural cycles. Moreover, programmed cycles also increased the risk of LGA (aOR = 1.459; 95% CI, 1.083–1.965; P = 0.013) but reduced the risk of SGA (aOR = 0.529; 95% CI, 0.348–0.805; P = 0.003) compared with minimal ovarian stimulation cycles. There were no significant differences between natural cycles and minimal ovarian stimulation cycles.ConclusionsDuring IVF/ICSI–FET treatment, the risk of HDP and LGA was increased in women with programmed cycles. Therefore, for patients with thin endometrium, irregular menstruation or no spontaneous ovulation, minimal ovarian stimulation cycles may be a relatively safer option than programmed cycles.

Is early-follicular long-acting GnRH agonist protocol an alternative for patients with polycystic ovary syndrome undergoing in vitro fertilization?

BackgroundWe aimed to compare the clinical and perinatal outcomes of patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment with either an early-follicular long-acting gonadotropin-releasing hormone agonist (GnRH-a) long protocol (EFLL) or a midluteal short-acting GnRH-a long protocol (MLSL).MethodsThis single–center, retrospective study, included patients with PCOS who underwent IVF/ICSI from January 2013 to June 2019 at the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Patients underwent either MLSL (1179 cycles) or EFLL (2390 cycles). The primary outcomes were pregnancy outcomes, perinatal and maternal complications.ResultsFresh embryo transfer (59.12% vs. 55.47%, P = 0.038), clinical pregnancy (75.23% vs. 53.82%, P = 0.001), and live birth rates (63.27% vs. 42.05%, P = 0.010) were higher in the EFLL group. However, the proportion of patients “freezing all" for high risk of ovarian hyperstimulation syndrome (OHSS) (24.27% vs. 32.06%, P = 0.001) and ectopic pregnancy (1.51% vs. 5.97%, P = 0.002) were lower in the EFLL group than in the MLSL group. The incidence of gestational diabetes was higher in the EFLL group than in the MLSL group (5.08% vs. 1.42%, RR 3.714, 95% confidence interval (CI) 1.474–9.360, P = 0.003). There were no significant differences in the incidence of hypertension, premature rupture of membranes, placenta previa, congenital heart disease, or neonatal weight between the two groups. Logistic regression results showed that age (OR 0.966, 95% CI 0.941–0.993, P = 0.013), treatments (OR 2.380, 95% CI 1.833–3.089, P = 0.001), and endometrial thickness on trigger day (OR 1.115, 95% CI 1.070–1.162, P = 0.001) were correlated with clinical pregnancy. Pre-pregnancy BMI (OR 1.098, 95% CI 1.002–1.204, P = 0.046), fasting plasma glucose (FPG) (OR 3.096, 95% CI 1.900–5.046, P = 0.001), and treatments (OR 3.458, 95% CI 1.359–8.800, P = 0.009) were correlated with gestational diabetes mellitus (GDM). Treatments (OR 0.291, 95% CI 0.148–0.575, P = 0.001) and endometrial thickness on trigger day (OR 0.834, 95% CI 0.722–0.962, P = 0.013) were correlated with ectopic pregnancy.ConclusionThe early-follicular long-acting GnRH agonist long protocol can be used as an ideal assisted reproductive technology (ART) pregnancy assistance program for patients with PCOS, but obese patients should be encouraged to lose weight before ART treatments to reduce the risk of GDM.

Comparison of an HCG-only trigger versus dual trigger for final oocyte maturation in a progestin-primed ovarian stimulation protocol

Research questionIs there any difference in clinical outcomes between a human chorionic gonadotrophin (HCG)-only trigger and a dual trigger combining gonadotrophin-releasing hormone agonist (GnRHa) and HCG in a progestin-primed ovarian stimulation (PPOS) protocol? DesignThis retrospective cohort study included women younger than 40 years old with a normal ovarian reserve who underwent IVF/intracytoplasmic sperm injection treatment with a PPOS protocol. Participants were allocated to two groups according to the triggering medicines. The clinical outcomes were compared, with cumulative live birth rate (CLBR) being the primary outcome. ResultsIn total, 1066 women were included, 565 in the HCG-only group and 501 in the dual trigger group. Demographic parameters were comparable between the groups. Fewer oocytes were retrieved in the HCG-only trigger group (dual trigger 12.56 ± 7.12 versus HCG-only trigger 11.62 ± 6.02, P = 0.020). No significant difference was observed in the numbers of two-pronuclear embryos (7.12 ± 4.90 versus 6.76 ± 4.45, P = 0.208) and high-quality embryos (4.01 ± 3.70 versus 3.96 ± 3.32, P = 0.815). The CLBR after one complete cycle was also similar (40.72% versus 43.72%, P = 0.354). Multivariate logistic analysis confirmed that the trigger method had no association with CLBR (odds ratio [OR] 0.763, 95% confidence interval [CI] 0.578–1.005, P = 0.055) in the PPOS-treated patients. ConclusionsCompared with the HCG-only trigger group, comparable embryological and clinical outcomes were achieved, although more oocytes were retrieved in the dual trigger group. This suggests that there may be no extra benefit from dual triggering, and that it should not be recommended for routine use in the general population undergoing PPOS protocols.

The relationship between coping strategies and infertility self-efficacy with pregnancy outcomes of women undergoing in vitro fertilization: A prospective cohort study.

BackgroundAssisted reproductive technology treatments are stressful procedures, but there are individual differences in the emotional response to them. Differences in response to this stress may be related to the outcome of infertility treatment.ObjectiveThis study aimed to investigate the relationship between coping strategies and infertility self-efficacy with pregnancy outcomes of women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment.Materials and MethodsThis was a prospective cohort study and the 154 infertile women were psychologically evaluated in 2 stages: once before ovarian stimulation and again during embryo transfer. The research measurements used were the Revised COPE, the Depression Anxiety Stress Scale (DASS-21) and the Infertility Self-Efficacy Scale.ResultsThere was no significant difference between the group of non-pregnant women and the positive pregnancy group in terms of coping strategies (mental rumination, self-blame, active confronting, goal replacement, avoidance) or self-efficacy in either of the 2 stages of ovarian stimulation and embryo transfer. The Mann-Whitney test did not show any statistical difference between the clinically pregnant women and the only laboratory positive pregnant group. Moreover, the self-blame and mental rumination strategies were positively related with anxiety and depression. Conversely, active confronting, goal replacement, avoidance and self-efficacy were associated with decreased depression, anxiety and stress levels.ConclusionIt can be concluded that there is no relationship between coping strategies and infertility self-efficacy with in vitro fertilization/intracytoplasmic sperm injection outcomes. Further research is needed to clarify the effects of other psychological factors on the pregnancy outcomes of assisted reproductive treatment.

New biopsy after antibiotic treatment: effect on outcomes of assisted reproduction in patients with infertility and chronic endometritis

Research questionWhat is the effect of chronic endometritis on patients with infertility, the necessity of endometrial re-examination and the effect of improving chronic endometritis after one cycle of antibiotic treatment on pregnancy outcomes? DesignInfertile patients (n = 4003) who underwent IVF and intracytoplasmic sperm injection treatment were included. Pregnancy outcomes of groups positive for chronic endometritis were compared with groups that were negative (group 1). Patients that were positive were divided into the chronic endometritis new biopsy group (group 2) and chronic endometritis non-re-examination group (group 3). After doxycycline treatment and re-examination, the chronic endometritis new biopsy group was divided into improved chronic endometritis group (ICE) and not-improved chronic endometritis group (NICE), and their general indicators and reproductive outcomes were compared. ResultsNo significant difference was observed in embryo implantation, early or late pregnancy loss, ectopic pregnancy, clinical pregnancy and live birth rates between groups 2 and 3. The clinical pregnancy and live birth rates in the NICE group were significantly lower than those in the ICE group (P = 0.008 and P = 0.001, respectively). After controlling for potential confounding factors, age, average number of high-quality embryos, endometrial thickness on the day of embryo transfer and number and type of embryo transfer were factors associated with live birth rates. ConclusionsEndometrial re-examination of women with chronic endometritis treated with doxycycline had no effect on pregnancy outcomes. The first cycle of doxycycline treatment could effectively improve reproductive outcomes of women with five or more CD138+ cells/high-power field.