Reproductive Medicine and Biology最新文献

Purpose: To evaluate the impact of Endometrial Microbiome Metagenomic Analysis and Analysis of Infectious Chronic Endometritis (EMMA & ALICE) on pregnancy outcomes following recommended treatments in women with recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL).

Methods: This prospective, multicenter cohort study included 527 women under 42 years old with RIF or RPL across 14 IVF centers in Japan. Endometrial samples were analyzed using EMMA & ALICE, and patients received antibiotics, probiotics, or no treatment based on test results. Pregnancy outcomes were assessed using Kaplan-Meier survival analysis and multivariate generalized linear models.

Results: Amongst participants, 43.4% had a normal Lactobacillus-dominated microbiota, 20.9% had dysbiosis, and 35.7% had mild dysbiosis or ultralow biomass. Kaplan-Meier analysis revealed significantly higher ongoing pregnancy rates in the dysbiosis group treated with antibiotics and probiotics compared to other groups (p = 0.031). Post-treatment, ongoing pregnancy rates in the dysbiosis and mild dysbiosis groups were comparable to the normal group.

Conclusions: EMMA & ALICE-guided antimicrobial and probiotic treatments improved pregnancy outcomes, enabling the dysbiosis group to achieve pregnancy earlier than the normal group. Addressing uterine dysbiosis may reduce the time to pregnancy in patients with RIF and RPL.

Trial registration: University Hospital Medical Information Network (UMIN), UMIN000036917.

Background: FIGLA is a transcription factor gene which plays a critical role in folliculogenesis. Consistent with this, FIGLA variants have been identified in females with non-syndromic primary ovarian insufficiency (POI) in both autosomal-dominant and autosomal-recessive forms.

Case description: We encountered two Japanese sisters who had secondary or primary amenorrhea at 15 years of age. They were diagnosed as having non-syndromic primary ovarian insufficiency (POI) with hypergonadotropic hypoestrogenism and markedly low serum anti-Müllerian hormone values.

Outcome: Whole genome sequencing revealed a novel homozygous missense variant, NM_001004311.3:c.338A>G:p.(Tyr113Cys), in FIGLA essential for folliculogenesis in the two sisters. The parents were heterozygous for this variant, and the heterozygous mother had regular menses at 51 years of age. This variant was extremely rare in public databases, and was invariably assessed as deleterious by six prediction tools. Furthermore, the p.(Tyr113Cys)-FIGLA protein was assessed as "pathogenic" or "likely pathogenic" by protein structural predictions, and was evaluated as "destabilizing" or "decrease stability" by protein stability predictions.

Conclusion: The results, in conjunction with the data reported in the literature, imply that FIGLA variants account for a small but certain fraction of non-syndromic POI, and pose a question as to the relevance of FIGLA variants to an autosomal dominant form of POI, although FIGLA variants have been identified in both autosomal dominant and autosomal recessive forms of non-syndromic POI.

Purpose: In vitro, oocyte development is susceptible to oxidative stress, which leads to endoplasmic reticulum (ER) stress. This study investigated whether the antioxidant melatonin attenuates ER stress and maintains oocyte-cumulus cell communication during the in vitro growth (IVG) of bovine oocytes.

Methods: Oocyte-granulosa cell complexes (OGCs) were harvested from slaughterhouse-derived ovaries and grown in vitro for 5 d at 38.5°C in 5% CO₂ humidified air. Melatonin (10^-7, 10^-9, or 10^-11 M) was added to the culture medium.

Results: Oocyte diameter increased on day 5 from its initial value in all groups. The antrum formation rate was significantly higher in the 10^-9 M melatonin-treated group than in the control. The melatonin-treated group showed reduced oxidative stress and increased gap junction communication compared with the control. ER stress-related genes in OGCs were significantly downregulated in the 10^-9 M melatonin-treated group compared with those in the control. No significant changes were found in subsequent maturation among groups; however, 10^-9 M melatonin treatment during IVG and IVM increased the maturation rate compared with that in the control.

Conclusions: Melatonin reduces oxidative stress, which attenuates ER stress in OGCs during IVG of bovine oocytes and may improve IVG efficiency in assisted reproductive technology.

Background: In vitro fertilization (IVF) and embryo transfer (ET) are widely used in reproductive biology. Despite the transfer of high-quality blastocysts, the implantation rate of IVF-derived blastocysts remains low after ET.

Methods: This article provides a comprehensive review of current research on embryo implantation regulators and their application to improve the implantation potential of IVF-derived blastocysts.

Main findings: The in vivo mouse model revealed selective proteolysis immediately after expression in activated blastocysts, that is, degradation of ERα expression in activated blastocysts regulated by the ubiquitin-proteasome pathway, followed by completion of blastocyst implantation. Treatment of blastocysts to induce appropriate protein expression during in vitro culture prior to ET is a useful approach for improving implantation rates. This approach showed that combined treatment with PRL, EGF, and 4-OH-E₂ (PEC) improved the blastocyst implantation rates. Furthermore, arginine and leucine drive reactive oxygen species (ROS)-mediated integrin α5β1 expression and promote blastocyst implantation.

Conclusion: Findings based on analysis of molecular and cellular regulators are useful for improving the implantation potential of IVF-derived blastocysts. These approaches may help to elucidate the mechanisms underlying the completion of the blastocyst implantation, although further investigation is required to improve the success of implantation and pregnancy.

Purpose: To compare risks of neonatal anomalies and obstetric complications among frozen-thawed embryo transfer (FET), fresh embryo transfer (FreshET), and non-assisted reproductive technology (non-ART) treatments in infertile women.

Methods: This retrospective cohort study analyzed 7378 singleton births (2643 non-ART, 4219 FET, 516 FreshET) from 2013 to 2022. Outcomes were compared using inverse probability weighting regression adjustment, with adjustment for maternal factors.

Results: After adjustment, the risk of neonatal anomalies did not differ significantly between FET and non-ART, or FreshET and non-ART. FET was associated with increased risks of obstetric complications compared with non-ART, including placenta accreta (adjusted risk difference [ARD] 3.61%, 95% CI 2.95-4.28), placenta previa (ARD 0.55%, 95% CI 0.14-0.96), postpartum hemorrhage (ARD 7.08%, 95% CI 6.03-8.13), gestational hypertension (ARD 3.57%, 95% CI 2.47-4.68), gestational diabetes (ARD 0.96%, 95% CI 0.17-1.75), and preterm birth (ARD 2.13%, 95% CI 1.23-3.02). FET also showed higher risk of high birth weight (ARD 0.97%, 95% CI 0.42-1.52). FreshET showed no significant differences in obstetric complications.

Conclusions: While the risk of neonatal anomalies did not differ among treatments, FET was associated with increased obstetric complication risks. These findings underscore the need for careful management of FET pregnancies and further research to improve treatment protocols.

Background: Polycystic ovary syndrome (PCOS) is a complex endocrinopathy, which leads to ovulation dysfunction and infertility, as well as metabolic and mental disorders. Women with PCOS exhibit several characteristic symptoms, with marked heterogeneity across different races and ethnicities.

Methods: In this review, the author outlines the phenotypic disparities of PCOS among various racial and ethnic populations. First, the prevalence of major symptoms in different racial and ethnic groups with PCOS is summarized. Next, the effects of four phenotypes, derived from the Rotterdam criteria for PCOS, on metabolic and reproductive features are recapitulated.

Main findings: A growing body of evidence suggests that East Asian populations exhibit less hirsutism and adiposity compared with other groups. However, hirsutism is more prevalent in South Asian, Middle Eastern, and Hispanic populations. Hispanic and African American populations have more frequent obesity and insulin resistance. With regard to the association between mental disorders and racial and ethnic differences, limited studies exist; therefore, no conclusions can be drawn.

Conclusion: Race and ethnicity-specific factors related to PCOS must be considered in clinical practice. The diagnostic criteria of PCOS should be specific to race and ethnicity to avoid missing treatment opportunities.

Background: As the COVID-19 pandemic nears resolution in 2024, the mechanisms by which SARS-CoV-2 and other viral infections induce spermatogenic dysfunction remain poorly understood. This review examines the mechanisms by which viral infections, particularly COVID-19, disrupt spermatogenesis and highlights the implications for male reproductive health. While reports suggest that spermatogenic dysfunction caused by COVID-19 is mild and transient, these findings may have broader applications in understanding and treating spermatogenic dysfunction caused by future viral infections.

Methods: The PubMed database was searched to identify original and review articles investigating the mechanisms by which viral infections, particularly SARS-CoV-2, contribute to spermatogenic dysfunction.

Main findings: SARS-CoV-2 affects the testis through multiple mechanisms, including ACE2 receptor-mediated entry, direct viral damage, inflammatory response, blood-testis barrier disruption, hormonal imbalance, oxidative stress, and impaired spermatogenesis. The combination of these factors can disrupt testicular function and highlights the complexity of the effects of COVID-19 on male reproductive health.

Conclusion: COVID-19 may disrupt spermatogenesis through direct testicular infection, systemic inflammation, hormonal disruption, and oxidative stress. Ongoing research, vaccination efforts, and clinical vigilance are essential to address these challenges and develop effective treatment and prevention strategies.

Purpose: Uterine leiomyomas (ULMs) are classified into those with and without MED12 mutations (MED12m(+) and MED12m(-), respectively). This study was undertaken to establish a culture system to evaluate the effect of female hormones on the growth of ULM cells in each ULM subtype.

Methods: ULM cells isolated from MED12m(+) or MED12m(-) tissues were cultured in a monolayer for 7 days with four hormone treatments: estrogen (E) and progesterone (P) (E + P), E only (E), P only (P), and medium only (CTRL). They were also cultured in a 3D spheroid culture system with the above four treatments and a fifth treatment: E + P + selective progesterone receptor modulator (E + P + SPRM). The hormonal effects were evaluated based on cell number, spheroid size, and histology.

Results: In the monolayer cultures, female hormones did not cause the proliferation of ULM cells of either subtype. In the spheroid cultures, spheroid sizes for both subtypes were significantly larger with the E + P and P treatments than with the CTRL and E treatments and were comparable in the E and E + P + SPRM treatments. Histological staining showed that collagen fibers were present only in the spheroids of the P-treated groups of MED12m(+).

Conclusion: We established a 3D spheroid culture system to evaluate the effects of female hormones on ULM cells.

Purpose: To investigate the effects of C-type natriuretic peptide (CNP) on human granulosa cell growth and elucidate its regulatory mechanisms.

Methods: A human non-luteinizing granulosa cell line (HGrC) developed from small antral follicles was used to assess the impact of CNP on cell proliferation and estrogen synthesis. cGMP production via the guanylate cyclase domain of the CNP receptor, natriuretic peptide receptor 2 (NPR2), was confirmed. The regulation of CNP encoding natriuretic peptide C (NPPC) and NPR2 by estradiol and oocyte-derived factors (ODFs) was examined.

Results: Besides detecting both NPPC and NPR2, CNP increased cellular proliferation. The specific action of CNP on cell proliferation was confirmed using siRNA transfection. CNP stimulated cGMP production, whereas a guanylate-cyclase inhibitor suppressed CNP-induced cell proliferation. Estradiol production was elevated by CNP treatment, accompanied by increased expression of estrogen synthetic enzymes. Furthermore, CNP upregulated NPR2 expression in cooperation with estradiol and ODFs, while estradiol increased NPPC expression.

Conclusion: This study demonstrates CNP stimulation of human granulosa cell growth and suggests potential cross-talk between these cells and oocytes. Further research on the simultaneous administration of CNP and estradiol may offer a promising approach for promoting early-stage follicle development in infertility treatments for patients with poor ovarian reserve.

Background: Embryologists are crucial in assisted reproductive technology (ART), yet their duties, education, and licensing requirements vary significantly across countries, complicating the determination of optimal staffing levels in ART laboratories. With anticipated advancements such as automation in ART laboratories, this review comprehensively analyzes factors necessary for appropriate future staffing.

Main findings: A comprehensive literature search was conducted using PubMed to identify relevant articles up to July 2024, employing keywords such as "embryologist," "staffing," and "certification." Articles were evaluated for content related to laboratory operations, and guidelines from five organizations regarding licensing and education were compared.

Results: The review revealed significant international differences in embryologist certification, duties, and staffing recommendations. These disparities, along with the integration of advanced ART technologies and regulatory requirements, significantly impact future staffing needs in ART laboratories.

Conclusion: The definitions of an ART cycle and required staffing levels vary across organizations, influenced by the certification and duties of embryologists in different countries. Adequate embryologist staffing is essential for ensuring laboratory quality control and impacting patient ART outcomes. As new technologies and automation reshape laboratory workflows, collaborative efforts among organizations, countries, and embryologist associations are essential for developing comprehensive educational curricula and determining appropriate staffing levels.