Progestin-Primed Ovarian Stimulation Protocol for Patients in Assisted Reproductive Technology: A Meta-Analysis of Randomized Controlled Trials.

Objectives: Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that can block the luteinizing hormone (LH) surge through progesterone instead of traditional down regulating or gonadotropin-releasing hormone (GnRH) antagonist, and in order to achieve multi-follicle recruitment. This paper aims to investigate the effectiveness of PPOS and its suitability for infertile patients with different ovarian reserve functions. Methods: We searched published randomized controlled trials (RCTs) about PPOS on Cochrane Library, PubMed, Embase, and Web of Science. The search period spanned from January 1, 2015 to November 16, 2020. The data were extracted, and the meta-analysis was performed on ovarian stimulation as well as embryological and clinical outcomes. The outcomes were pooled by a random effects model, and the risk of heterogeneity was evaluated. Subgroup analysis was performed for different ovarian reserve patients. Results: The clinical pregnancy rates and live birth or ongoing pregnancy rates with the PPOS protocol were not different from those with the control group. In the diminished ovarian reserve (DOR) subgroup, the PPOS protocol had a lower rate of premature LH surge [RR = 0.03, 95% CI = 0.01 to 0.13, p < 0.001]. The PPOS protocol had a lower rate of ovarian hyperstimulation syndrome (OHSS) [RR = 0.52, 95% CI = 0.36 to 0.76, p < 0.001, I2 = 0.00%]. The secondary outcomes showed that the number of oocytes retrieved, MII oocytes, and viable embryos was higher than that of the control protocol in DOR patients [(MD = 0.33, 95% CI = 0.30 to 0.36, p < 0.001), (MD = 0.30, 95% CI = 0.27 to 0.33, p < 0.001), (MD = 0.21, 95% CI = 0.18 to 0.24, p < 0.001)] and normal ovarian reserve (NOR) patients [(MD = 1.41, 95% CI = 0.03 to 2.78, p < 0.001), (MD = 1.19, 95% CI = 0.04 to 2.35, p < 0.001), (MD = 1.01, 95% CI = 0.21 to 1.81, p = 0.01)]. Conclusion: The findings suggest that PPOS is an effective ovarian stimulation protocol and is beneficial for patients with different ovarian reserve functions, which needs to be validated in more RCTs with larger samples.

Identification of Significant Predictors for the Need of Insulin Therapy and Onset of Postpartum Impaired Glucose Tolerance in Gestational Diabetes Mellitus Patients.

BACKGROUND: Gestational diabetes mellitus (GDM) during pregnancy can greatly increase the risk for a number of adverse prenatal and postpartum consequences, including postpartum impaired glucose tolerance (IGT). Determining the need for insulin therapy is critical for controlling the glycemic level in GDM patients. The study contains two major purposes: 1) to identify the potential predictors for the need of insulin therapy in GDM patients; 2) to identify the factors that are related to the onset of postpartum IGT. MATERIALS AND METHODS: Here, we performed a retrospective study on 112 GDM patients in China to identify the significant predictors for the need of insulin therapy and onset of postpartum IGT in patients with GDM. RESULTS: Age and gestational weeks at GDM diagnosis, pregestational BMI, family history of diabetes mellitus (DM), plasma glucose levels assessed by 75-g OGTT at both the 1-hour and 2-hour time points (PG-1h and PG-2h) and HbA1c level were all significantly different between the patients that received insulin therapy and those did not. During postpartum, family history of DM, PG-1h PG-2h and HbA1c level were found to be significantly different between the patients with normal glucose tolerance and those with IGT. CONCLUSION: Our results reveal a number of factors that are closely associated with the need of insulin therapy and onset of postpartum IGT, especially the PG-1h and PG-2h levels. These findings will provide valuable indications on selection of treatment strategy for GDM and GDM-induced postpartum IGT.

Microinjection manipulation decreases the expression of GABA-A receptor signaling pathway genes in mouse embryos derived using intracytoplasmic sperm injection.

BACKGROUND: The GABA-A receptor signaling pathway regulates proliferation, differentiation, apoptosis, and responses to overt DNA damage during embryonic development. METHODS: To analyze the gene expression after intracytoplasmic sperm injection (ICSI) and in in vivo mouse embryos, the global pattern of gene expression dataset, GSE23009, was obtained from the Gene Expression Omnibus database. Genes with differential expression were identified using the R software package, and RT-qPCR was performed to confirm the microarray results. RESULTS: Mouse blastocysts derived from ICSI fertilization had decreased expression of GABA-A receptor signaling pathway genes. However, the mechanisms underlying these changes were not elucidated. The gene expression of the GABA-A pathway was not significantly different between blastocysts obtained from IVF and in vivo fertilization. However, microinjection after IVF significantly reduced the expression of the GABA-A pathway gene to levels similar to those in the ICSI group. CONCLUSION: Based on our results, decreased gene expression is a result of the microinjection manipulation performed during ICSI.

Whole-exome sequencing of a large Chinese azoospermia and severe oligospermia cohort identifies novel infertility causative variants and genes.

Rare coding variants have been proven to be one of the significant factors contributing to spermatogenic failure in patients with non-obstructive azoospermia (NOA) and severe oligospermia (SO). To delineate the molecular characteristics of idiopathic NOA and SO, we performed whole-exome sequencing of 314 unrelated patients of Chinese Han origin and verified our findings by comparing to 400 fertile controls. We detected six pathogenic/likely pathogenic variants and four variants of unknown significance, in genes known to cause NOA/SO, and 9 of which had not been earlier reported. Additionally, we identified 20 novel NOA candidate genes affecting 25 patients. Among them, five (BRDT, CHD5, MCM9, MLH3 and ZFX) were considered as strong candidates based on the evidence obtained from murine functional studies and human single-cell (sc)RNA-sequencing data. These genetic findings provide insight into the aetiology of human NOA/SO and pave the way for further functional analysis and molecular diagnosis of male infertility.

Glutathione S-transferase P1 Ile105Val Polymorphism and Male Infertility Risk: An Updated Meta-analysis.

BACKGROUND: Several studies concerning the association between glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and male infertility risk have reported controversial findings. The present study was aimed to explore this association using a meta-analysis. METHODS: The PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched. Odds ratios (OR s) with 95% confidence intervals (CI s) were calculated to estimate the strength of the association. RESULTS: A total of 3282 cases and 3268 controls in nine case-control studies were included. There was no significant association between GSTP1 Ile105Val polymorphism and male infertility in the overall population, but significant associations were found under the dominant (OR = 1.23, 95% CI = 1.04-1.46, I2 = 32.2%) and heterozygote (OR = 1.29, 95% CI = 1.08-1.53, I2 = 26.8%) models after excluding studies for which the data did not satisfy Hardy-Weinberg equilibrium (HWE). Similarly, subgroup analyses revealed no significant association in Asians or Chinese population although a significant association was apparent among Chinese population in studies with HWE under the heterozygote model (OR = 1.25, 95% CI = 1.03-1.52, I2 = 44.1%). Significant heterogeneity could be observed in some genetic models, but this heterogeneity was not significant when stratified by HWE. No evidence for publication bias was found. CONCLUSIONS: The GSTP1 Ile105Val polymorphism might not be associated with male infertility risk, and thus additional well-designed studies with larger sample size are warranted.

[Qilin Pills for idiopathic oligoasthenospermia: A multi-centered randomized double-blind controlled clinical trial].

OBJECTIVE: To evaluate the clinical efficacy and safety of Qilin Pills in the treatment of oligoasthenospermia in infertile men. METHODS: This multi-centered randomized double-blind controlled clinical trial included 216 infertile males with oligoasthenospermia, 108 in the trial group and the other 108 in the control, the former treated with Qilin Pills at the dose of 6 g tid while the latter with Wuziyanzong Pills at 6 g bid, both for 12 weeks. We examined the total sperm count, sperm motility and the count of progressively motile sperm of the patients before and at 4, 8 and 12 weeks after medication and evaluated the safety of the drug based on the adverse events and the laboratory results of blood and urine routine examinations and liver and kidney function tests. RESULTS: Compared with the baseline, the patients in the trial group showed a significant time-dependent improvement after 4, 8 and 12 weeks of medication in sperm motility (21.75% vs 27.54%, 29.04% and 32.95%, P <0.05), total sperm count (156.27 ×106 vs 177.33, 188.18 and 205.44 ×106, P <0.05), and the count of progressively motile sperm (32.08 ×106/ml vs 46.33, 50.98 and 61.10 ×106/ml, P <0.05). The three parameters above were also improved in the controls, but more significantly in the trial group (P <0.05). CONCLUSIONS: Qilin Pills can evidently improve the semen quality of oligoasthenospermia patients with no obvious adverse events.

[Reliability and validity of the Chinese version of The Premature Ejaculation Diagnostic Tool].

OBJECTIVE: To translate the English version of The Premature Ejaculation Diagnostic Tool (PEDT) into Chinese, evaluate its reliability and validity, and analyze its feasibility in the diagnosis of premature ejaculation (PE). METHODS: Following the forward-backward translation procedure, we developed the Chinese version of PEDT, which was then revised by andrologists and bilingual linguists. We enrolled subjects with or without PE from 15 urological or andrological clinics in China and obtained the information about their demographic characteristics, PEDT scores, and intra-vaginal ejaculation latency time (IELT). We evaluated the internal consistency of PEDT using Cronbach alpha, was examined its reliability and stability by test-retest analysis, analyzed its correlation with IELT by Spearman correlation analysis, and tested its sensitivity and specificity by receiver operating characteristic ( ROC) analysis. RESULTS: Totally, 570 PE patients (aged [30.66 ± 7.11] years) and 226 non-PE men (aged [33.01 ± 5.41] years) were recruited, with the mean IELT of (1.34 ± 0.54) min in the former and (11.09 ± 7.5) min in the latter group. The Cronbach's alpha of the Chinese version of PEDT was 0.79, and the test-retest correlation coefficient was 0.75 (P < 0.01). The PEDT score was negatively correlated with IELT (Spearman's p = -0.52, P < 0.01). When the cutoff value of PE diagnosis was defined as 7.5, the sensitivity and specificity of PEDT were 0.80 and 0.78, and when as 8.5, they were 0.72 and 0.89, respectively. CONCLUSION: The Chinese version of PEDT was demonstrated to have good internal consistency, reliability, and validity, as well as a high predictability for PE. It can be used as a reliable and convenient tool to screen PE among Chinese men.

[Ouabain and asthenospermia].

Asthenospermia accounts for about 30% of the causes of male infertility. Currently, most drugs for asthenospermia lack specificity and desirable therapeutic efficiency. An insight into the pathogenesis of asthenospermia is important for the development of specific therapies for this disease. The protein Na+/K(+)- ATPase α4 isoform (NKA4) presents in both mature testis tissue and the sperm tail, the absence or reduced activity of which may significantly decrease sperm motility. Ouabain is a natural inhibitor of NKA4, suppressing its activity by specifically binding the ouabain site in it. The hypothalamus and adrenal cortex excrete an ouabain-like steroid hormone called endogenous ouabain (EO), which may be associated with the pathogenesis of asthenospermia by inhibiting the activity of NKA4, affecting Na+/H+ exchange, Na+/Ca2+ exchange and sperm cell membrane potential, and eventually reducing sperm motility.

Complete hydatidiform mole and a coexistent fetus following ovulation induction in a patient with Sheehan's syndrome: a first case report and review of literature.

Pregnancy in Sheehan's syndrome (SS) is extremely rare. We present the first reported case of twin pregnancy with complete hydatiform mole (CHM) and a coexistent fetus (CHCF) in a patient with SS. A 29-year-old Chinese patient with SS became pregnant following one cycle of ovulation induction with human menopausal gonadotropin after secondary infertility. A normal live fetus and a low echogenic mass suspected hydatidiform mole (HM) were detected by ultrasound examinations at gestational week 8. The couple highly desired to continue the pregnancy because it is very hard to get pregnant for the patients with SS. However, the pregnancy was terminated for the size of the HM component increased rapidly at gestational week 15. Histological examinations confirmed CHCF. Genetic studies showed that the CHM genome was derived from paternal diploidy, and the normal fetus was from biparental genomes. Furthermore, a literature review on these topics is included. This case highlighted that even in a patient with SS, twin pregnancy with CHCF can still occur after ovulation induction.

[Sperm DNA integrity of infertile males with hepatitis B virus infection].

OBJECTIVE: To investigate sperm DNA integrity in male infertility patients with hepatitis B virus (HBV) infection. METHODS: This study included 90 infertile men with HBV infection (group A), 82 infertile men without HBV infection (group B) and 70 normal fertile men (group C). We detected sperm DNA integrity among the subjects, including DNA fragmentation index (DFI) and high DNA stainability (HDS), by sperm chromatin structure assay (SCSA), and compared them among the three groups. RESULTS: DFI was higher in group A ([28.17 +/- 13.06]%) than in B ([26.64 +/- 9.79]%) and C ([15.67 +/- 4.73]%), significantly higher in A and B than in C (P < 0.05) but with no significant difference between A and B (P > 0.05). HDS was higher in group A ([10.83 +/- 5.601]%) than in B ([9.04 +/- 3.48]%) and C ([8.04-2.25]%), with significant difference between A and C (P < 0.05). CONCLUSION: Sperm DNA integrity of infertile males is significantly different from that of normal fertile men, and infertility with HBV infection further impairs sperm DNA, which is manifested by abnormal sperm nuclear maturity.

[Qianlie Beixi Capsules for unliquefiable semen: a multi-center clinical study].

OBJECTIVE: To investigate the efficacy and possible action mechanism of Qianlie Beixi Capsules in the treatment of unliquefiable semen. METHODS: A total of 190 patients with unliquefiable semen were treated with Qianlie Beixi Capsules for 1 or 2 courses (3 weeks per a course). The seminal changes were observed and recorded. RESULTS: Of the 190 patients in the 1-course treatment arm, 99 were cured and 91 failed to respond after the first course. And the effectiveness rate was 52.1%. Of the 122 patients in the 2-course treatment arm, 81 were cured and 41 failed to respond after the second course. And the effectiveness rate was 66.4%. The efficacy of 2-course regimen was obviously better than that of 1-course regiment. In the meantime, sperm density improved in the 2-course treatment arm. Sperm motility improved slightly in the effective subjects of 1-course treatment arm. All the above results had statistically significant differences (P < 0.05). CONCLUSION: Qianlie Beixi Capsules is both safe and effective for unliquefiable semen and may shorten the time of seminal liquefaction.