Altered zygotic gene expression caused by sperm with variants disrupts early embryonic development.

The precise mechanisms behind early embryonic arrest due to sperm-related factors and the most effective strategies are not yet fully understood. Here, we present two cases of male infertility linked to novel variants, associated with oligoasthenoteratozoospermia (OAT) and early embryonic arrest. To investigate the underlying mechanisms and promising therapeutic approaches, knock-in and knock-out mice were generated.

Earlier second polar body transfer and further mitochondrial carryover removal for potential mitochondrial replacement therapy.

The second polar body (PB2) transfer in assisted reproductive technology is regarded as the most promising mitochondrial replacement scheme for preventing the mitochondrial disease inheritance owing to its less mitochondrial carryover and stronger operability. However, the mitochondrial carryover was still detectable in the reconstructed oocyte in conventional second polar body transfer scheme. Moreover, the delayed operating time would increase the second polar body DNA damage.

Neonatal outcomes and congenital malformations in children born after progestin-primed ovarian stimulation protocol.

Purpose: The purpose of this study is to assess the safety of progestin-primed ovarian stimulation (PPOS) protocol regarding the neonatal outcomes and congenital malformations in babies born after fertilization (IVF) and frozen embryo transfer (FET).

Methods: In this large retrospective cohort study, a total of 16,493 infants born between 1 September 2013 and 31 July 2021 from IVF and FET cycles after treatment with either PPOS (n = 15,245) or gonadotropin-releasing hormone antagonist (GnRH-ant) (n = 1,248) were finally enrolled. The primary outcome measure was the incidence of congenital malformations.

A follow-up study on congenital anomalies in 2208 offspring of three years old born after luteal-phase stimulation.

Research Question: What is the long-term safety in terms of congenital anomalies of a luteal-phase stimulation (LPS) protocol?

Design: In this cohort study, 664 couples and their children born after LPS and 1308 couples and their children born after a short agonist protocol were recruited. To investigate the long-term safety of LPS in terms of the prevalence of congenital anomalies, the physical growth and the health status of the offspring, the follow-up was divided into three steps: preparations before follow-up, first-stage follow-up including four telephone interviews, and second-stage follow-up when the children were aged 3 years.

Results: The total prevalence of congenital anomalies did not differ between groups.

Differences in Ectopic Pregnancy Rates between Fresh and Frozen Embryo Transfer after In Vitro Fertilization: A Large Retrospective Study.

Ectopic pregnancy (EP) is increasingly found in women treated with in vitro fertilization and embryo transfer (IVF−ET). With the development of the freeze-all policy in reproductive medicine, it is controversial whether frozen embryo transfer (FET) could reduce the rate of EP. In this single-center, large-sample retrospective study, we analyzed 16,048 human chorionic gonadotrophin (hCG)-positive patients who underwent fresh embryo transfer (ET) or FET cycles between January 2013 and March 2022.

miR-196a-5p-Rich Extracellular Vesicles from Trophoblasts Induce M1 Polarization of Macrophages in Recurrent Miscarriage.

Purpose: Numerous studies have described the presence of crosstalk between trophoblasts and macrophages and the critical role it plays in recurrent miscarriage (RM). However, the mechanism of trophoblast-derived extracellular vesicle (EV) miRNAs and their interactions with decidual macrophages in the pathogenesis of RM remains unclear.

Materials And Methods: miRNA-seq was used to identify the differentially expressed miRNAs between RM patients and healthy controls.

Luteinizing Hormone Suppression by Progestin-Primed Ovarian Stimulation Is Associated With Higher Implantation Rate for Patients With Polycystic Ovary Syndrome Who Underwent Fertilization/Intracytoplasmic Sperm Injection Cycles: Comparing With Short Protocol.

Background: Many studies have demonstrated the positive clinical value of progestin-primed ovarian stimulation (PPOS) in patients with polycystic ovary syndrome (PCOS) who underwent assisted reproductive technology. However, the underlying factors contributing to this phenomenon remain unclear. We conducted a retrospective observational study to compare the clinical outcomes of women with PCOS who underwent PPOS or the short protocol to identify possible factors that influence the outcome.

Frozen Embryo Transfer in Mildly Stimulated Cycle With Letrozole Compared to Natural Cycle in Ovulatory Women: A Large Retrospective Study.

Objective: To evaluate the clinical effect of mild stimulation with letrozole on pregnancy outcomes in ovulatory women undergoing frozen embryo transfer (FET) compared to natural cycle.

Design: Retrospective observational study.

Setting: Tertiary care academic medical center.

Progesterone affects clinic oocyte yields by coordinating with follicle stimulating hormone via PI3K/AKT and MAPK pathways.

Introduction: As an effective inhibitor of premature ovulation, progestin was introduced to a novel ovarian stimulation regimen for infertility treatment. However, the local action of progestin on the ovary and its effect on clinical outcomes have not been described.

Objectives: The influence of progesterone administration on clinical oocyte outcomes and the mechanisms involved in the coordination of progesterone and follicle stimulating hormone (FSH) on follicle growth and oocyte yields were investigated.

TIGIT-Fc as a Potential Therapeutic Agent for Fetomaternal Tolerance.

The perfect synchronization of maternal immune-endocrine mechanisms and those of the fetus is necessary for a successful pregnancy. In this report, decidual immune cells at the maternal-fetal interface were detected that expressed TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is a co-inhibitory receptor that triggers immunological tolerance. We generated recombinant TIGIT-Fc fusion proteins by linking the extracellular domain of TIGIT and silent Fc fragments.

Significance of endometrial thickness change after human chorionic gonadotrophin triggering in modified natural cycles for frozen-thawed embryo transfer.

Background: Peak endometrial thickness (EMT), measured on the end of follicular phase or early luteal phase, is the most widely used marker for endometrial receptivity during infertility treatment. However, the clinical significance of follicular-to-luteal EMT change remains unclear. We aimed to study whether the change of EMT between the day of human chorionic gonadotrophin (hCG) triggering and the day of frozen-thawed embryo transfer (FET) has any influence on pregnancy outcomes in modified natural cycles (mNCs).

Effect of Endometrial Thickness Change in Response to Progesterone Administration on Pregnancy Outcomes in Frozen-Thawed Embryo Transfer: Analysis of 4465 Cycles.

Objective: To evaluate whether endometrial thickness (EMT) change in response to progesterone has an effect on pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles.

Design: Retrospective observational study.

Setting: Tertiary-care academic medical center.

Value of endometrial thickness change after human chorionic gonadotrophin administration in predicting pregnancy outcome following fresh transfer in vitro fertilization cycles.

Purpose: To study whether the change of endometrial thickness (EMT) between the day of human chorionic gonadotrophin (hCG) administration and the day of embryo transfer has any impact on pregnancy outcome in fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles.

Methods: This single-center retrospective cohort study included 2620 patients undergoing their first consecutive autologous IVF/ICSI cycles from January 2003 to December 2012. Patients were categorized into three groups based on the percentage change of post-hCG EMT: > 10% decrease, ± 10% plateau and > 10% increase.

Adherence to healthy dietary patterns and outcomes of assisted reproduction: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the association between adherence to a healthy dietary pattern and outcomes of assisted reproductive techniques (ARTs). PubMed, Embase and Web of Science were searched for eligible studies through December 2019 according to the population, intervention, comparison, outcome and study design (PICOS) criteria. Eight prospective cohort studies (S) reporting pregnancy outcomes (O) of higher lower adherence to a healthy dietary pattern (I/C) in women undergoing ART treatment (P) were included, involving a total of 2229 women with 2067 embryo transfer cycles.

Delayed versus immediate frozen embryo transfer after oocyte retrieval: a systematic review and meta-analysis.

Purpose: This systematic review and meta-analysis aimed to compare pregnancy outcomes between immediate frozen embryo transfer (FET) performed within the first menstrual cycle after oocyte retrieval and delayed FET following subsequent cycles.

Methods: PubMed, EMBASE, and Web of Science were searched for eligible studies through January 2020. The main outcome measures were clinical pregnancy rate (CPR), live birth rate (LBR), and pregnancy loss rate (PLR).

Association between endometrial thickness and neonatal outcomes in intrauterine insemination cycles: a retrospective analysis of 1,016 live-born singletons.

Background: Decreased endometrial thickness (EMT) has been suggested to be associated with reduced birthweight of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) newborns. Considering the differences in ovarian stimulation degree and laboratory procedures between IVF/ICSI and IUI treatment, we aim to investigate whether EMT has any influence on IUI infant outcomes as well.

Methods: This was a retrospective cohort study of 1016 patients who had singleton livebirths after IUI treatment cycles from January 2008 to December 2018 at a tertiary-care academic medical center in China.

Effect of a prior cesarean delivery on pregnancy outcomes of frozen-thawed embryo transfer: A retrospective cohort study in a freeze-all setting.

Introduction: The association between the mode of previous delivery and subsequent success of assisted reproductive treatment has been poorly understood. By mitigating the detrimental effect of supraphysiologic estradiol levels on endometrial receptivity, a freeze-all strategy provides a novel model to investigate the sole impact of a prior cesarean delivery (CD) on embryo transfer outcomes.

Material And Methods: This single-center retrospective cohort study included 2660 patients who underwent their first frozen-thawed embryo transfer cycles after a freeze-all policy from January 2013 to December 2018.

Therapeutic role of granulocyte macrophage colony-stimulating factor (GM-CSF) in patients with persistent thin endometrium: A prospective and randomized study.

Objective: To assess the effect of granulocyte macrophage colony-stimulating factor (GM-CSF) on unresponsive thin (<7 mm) endometrium in women undergoing frozen-thawed embryo transfer.

Methods: A single-center, randomized, prospective study enrolled 304 women with thin unresponsive endometrium from Shanghai Ninth People's Hospital between March 2017 and May 2018. Of them, 161 patients received an intrauterine infusion of GM-CSF and 143 patients served as controls.

Hypoxia Promotes Vascular Smooth Muscle Cell (VSMC) Differentiation of Adipose-Derived Stem Cell (ADSC) by Regulating Mettl3 and Paracrine Factors.

Adipose-derived stem cell (ADSC) is an alternative and less invasive source of mesenchymal stem cells which can be used to develop biological treatment strategies for tissue regeneration, and their therapeutic applications hinge on an understanding of their physiological characteristics. N6-Methyladenosine (m6A) is the most common chemical modification of mRNAs and has recently been revealed to play important roles in cell lineage differentiation and development. However, the role of m6A modification in the vascular smooth muscle cell (VSMC) differentiation of ADSCs remains unclear.

Progestin-Primed Ovarian Stimulation with Dydrogesterone versus Medroxyprogesterone Acetate in Women with Polycystic Ovarian Syndrome for in vitro Fertilization: A Retrospective Cohort Study.

Purpose: Dydrogesterone (DYG) is an alternative progestin in progestin-primed ovarian stimulation (PPOS) protocol with weaker pituitary suppression than medroxyprogesterone acetate (MPA) in normal ovulatory women. However, the endocrinological characteristics, oocyte retrieval and pregnancy outcomes of DYG application in polycystic ovarian syndrome (PCOS) patients undergoing in vitro fertilization (IVF) remain unclear.

Patients And Methods: This retrospective cohort study included 420 PCOS patients who underwent controlled ovarian stimulation with human menopausal gonadotropin (hMG) and DYG (n=105) or MPA (n=315) from January 2014 to December 2017.

Association between peak serum estradiol level during controlled ovarian stimulation and neonatal birthweight in freeze-all cycles: a retrospective study of 8501 singleton live births.

Study Question: Is there an association between peak serum estradiol (E2) level during controlled ovarian stimulation (COS) and neonatal birthweight in freeze-all cycles?

Summary Answer: Peak serum E2 level during ovarian stimulation is not associated with neonatal birthweight in freeze-all cycles.

What Is Known Already: Supraphysiologic E2 levels during COS have been demonstrated to generate a suboptimal peri-implantation endometrial environment and thus lead to adverse neonatal outcomes in fresh embryo transfer cycles. Previous experimental studies also suggested a potential influence of superovulation on oocyte epigenetic programming, but whether it translates into altered phenotypes of fetal growth and development remains unclear in clinical practice.

Timing of frozen-thawed embryo transfer after controlled ovarian stimulation in a non-elective freeze-all policy.

Background: Non-elective freeze-all policy has been increasingly utilized in assisted reproductive treatment, but the optimal timing of frozen-thawed embryo transfer (FET) after controlled ovarian stimulation (COS) remains to be investigated.

Methods: This retrospective cohort study included 2,998 patients who underwent their first FETs after the first COS cycles using the non-elective freeze-all strategy from Jan 2013 to Dec 2016 at a tertiary-care academic medical center. Patients were divided into the "immediate" group in which FET took place within the first menstrual cycle after oocyte retrieval, and the "delayed" group where FET started after one or more menstrual cycles following COS.

Effect of Maternal Age on Pregnancy or Neonatal Outcomes Among 4,958 Infertile Women Using a Freeze-All Strategy.

The freeze-all strategy has been increasingly employed in the context of fertilization (IVF) cycles globally, but the relative advantages of this approach are not entirely understood. Herein we sought to assess how maternal age affected pregnancy and neonatal outcomes in women who had undergone frozen-thawed embryo transfer (FET). In this retrospective analysis, we assessed outcomes for 4,958 total women at the University-affiliated Tertiary Centre from January-December 2017.

Effect of Switching from a Progestin-Primed Ovarian Stimulation Protocol to a Modified Ultra-Long Protocol Among Women Who Had 1 Progestin-Primed Ovarian Stimulation (PPOS) Failure Verses Those Who Had 2 PPOS Failures.

BACKGROUND There is little research on whether normoresponsive patients who produced poor-quality embryos once verses those who produced poor-quality embryos twice when using a single COH protocol should change to a different controlled ovarian hyperstimulation (COH) protocol. MATERIAL AND METHODS In this retrospective study, we enrolled 108 patients with 1 PPOS failure who chose to continue receiving the progestin-primed ovarian stimulation (PPOS) protocol (n=61) versus those who decided to switch to the modified ultra-long protocol (n=47). We also enrolled 131 normoresponsive patients with 2 PPOS failures who chose to continue receiving the PPOS protocol (n=60) versus those who decided to switch to the modified ultra-long protocol (n=71) in the third cycle.

Cross-linked hyaluronan gel to improve pregnancy rate of women patients with moderate to severe intrauterine adhesion treated with IVF: a randomized controlled trial.

Purpose: To evaluate whether the cross-linked hyaluronan (cHA) gel can improve the clinical pregnancy rate of patients with moderate to severe intrauterine adhesion (IUA) who underwent operative hysteroscopy followed by embryo transfer.

Methods: Women with moderate to severe IUA desiring to undergo embryo transfer were recruited in this randomized controlled trial. The patients were randomized on the day of receiving hysteroscopy.