In vitro fertilization, intracytoplasmic sperm injection, in vitro maturation, and embryo culture.

Infertility is a highly prevalent disease affecting 1 in 6 couples worldwide. While there are numerous treatment options available to treat infertility, fertilization (IVF) is the most successful therapy available. IVF traditionally involves superovulation of the ovaries followed by ultrasound (US)-guided oocyte retrieval, fertilization of oocytes and culture of resultant embryos.

Cellular heterogeneity and dynamics of the human uterus in healthy premenopausal women.

The human uterus is a complex and dynamic organ whose lining grows, remodels, and regenerates every menstrual cycle or upon tissue damage. Here, we applied single-cell RNA sequencing to profile more the 50,000 uterine cells from both the endometrium and myometrium of five healthy premenopausal individuals, and jointly analyzed the data with a previously published dataset from 15 subjects. The resulting normal uterus cell atlas contains more than 167K cells, representing the lymphatic endothelium, blood endothelium, stromal, ciliated epithelium, unciliated epithelium, and immune cell populations.

Progestogen-driven B7-H4 contributes to onco-fetal immune tolerance.

Immune tolerance mechanisms are shared in cancer and pregnancy. Through cross-analyzing single-cell RNA-sequencing data from multiple human cancer types and the maternal-fetal interface, we found B7-H4 (VTCN1) is an onco-fetal immune tolerance checkpoint. We showed that genetic deficiency of B7-H4 resulted in immune activation and fetal resorption in allogeneic pregnancy models.

The impact of obesity on reproductive health and metabolism in reproductive-age females.

Obesity is a highly prevalent chronic disease that impacts >40% of reproductive-aged females. The pathophysiology of obesity is complex and can be understood simply as a chronic energy imbalance whereby caloric intake exceeds caloric expenditure with an energy surplus stored in adipose tissue. Obesity may be categorized into degrees of severity as well as different phenotypes on the basis of metabolic health and underlying pathophysiology.

Cellular heterogeneity and dynamics of the human uterus in healthy premenopausal women.

Unlabelled: The human uterus is a complex and dynamic organ whose lining grows, remodels, and regenerates in every menstrual cycle or upon tissue damage. Here we applied single-cell RNA sequencing to profile more the 50,000 uterine cells from both the endometrium and myometrium of 5 healthy premenopausal individuals, and jointly analyzed the data with a previously published dataset from 15 subjects. The resulting normal uterus cell atlas contains more than 167K cells representing the lymphatic endothelium, blood endothelium, stromal, ciliated epithelium, unciliated epithelium, and immune cell populations.

Proteomic analysis of human sperm reveals changes in protamine 1 phosphorylation in men with infertility.

Objective: To perform a comprehensive assessment of protamine (P) isoforms and modifications in human sperm with the aim of identifying how P modifications and isoforms are altered in men with reduced sperm motility and low sperm count.

Design: Cross-sectional.

Setting: Academic medical center.

Obesity and In Vitro Fertilization.

Obesity is a highly prevalent chronic disease with a significant effect on reproductive-age women. The clinical implications of obesity on fertility and pregnancy are well studied citing ovulatory dysfunction, hormonal imbalances, higher miscarriage rates, and increased maternal and neonatal risks. For this reason, many patients with obesity seek reproductive specialists to help build their families.

Sperm chromatin structure and reproductive fitness are altered by substitution of a single amino acid in mouse protamine 1.

Conventional dogma presumes that protamine-mediated DNA compaction in sperm is achieved by electrostatic interactions between DNA and the arginine-rich core of protamines. Phylogenetic analysis reveals several non-arginine residues conserved within, but not across species. The significance of these residues and their post-translational modifications are poorly understood.

Total fertilization failure with in vitro fertilization-intracytoplasmic sperm injection related to WEE2 mutation highlights emerging importance of genetic causes of in vitro fertilization failure.

Objective: To report a unique case of total fertilization failure (TFF) after in vitro fertilization with intracytoplasmic sperm injection related to homozygous gene mutation and summarize the current literature and management of TFF.

Design: Case report.

Setting: Academic fertility center.

Obesity-related alterations in protein expression in human follicular fluid from women undergoing in vitro fertilization.

Objective: To compare the proteomic composition of follicular fluid from women with normal weight vs. women with obesity but without a history of polycystic ovary syndrome or known ovarian dysfunction undergoing in vitro fertilization.

Design: Cross-sectional.

Obesity-induced follicular phase endometrial proteome dysregulation in a well-phenotyped population.

Objective: Despite obesity's significant impact on reproduction, its influence on the physiology of the human endometrium is largely understudied. We hypothesized that endometrial proteomic differences exist between obese (OW; body mass index [BMI] ≥30 kg/m) and normal-weight women (NWW; BMI, 18.5-24.

Sperm centriole assessment identifies male factor infertility in couples with unexplained infertility - a pilot study.

Unexplained infertility affects about one-third of infertile couples and is defined as the failure to identify the cause of infertility despite extensive evaluation of the male and female partners. Therefore, there is a need for a multiparametric approach to study sperm function. Recently, we developed a Fluorescence-Based Ratiometric Analysis of Sperm Centrioles (FRAC) assay to determine sperm centriole quality.

Cellular heterogeneity of human fallopian tubes in normal and hydrosalpinx disease states identified using scRNA-seq.

Fallopian tube (FT) homeostasis requires dynamic regulation of heterogeneous cell populations and is disrupted in infertility and ovarian cancer. Here, we applied single-cell RNA-seq to profile 59,738 FT cells from four healthy, pre-menopausal subjects. The resulting cell atlas contains 12 major cell types representing epithelial, stromal, and immune compartments.

Outcomes of subchorionic hematoma-affected pregnancies in the infertile population.

Objective: To determine the implications of an incidentally noted subchorionic hematoma on pregnancy outcomes in the infertile population.

Methods: Retrospective cohort study at a tertiary care, university-based facility. All patients with intrauterine pregnancy on initial obstetric ultrasound presenting to an infertility clinic between January 2015 and March 2018 (n = 1210), regardless of treatment cycle, were included.

Establishing a reproductive biorepository for basic and translational research: experience developing the reproductive subjects registry and sample repository.

Purpose: To report experience designing and establishing a reproductive registry and sample biorepository and to describe initial subject characteristics and biospecimens.

Methods: Beginning in December 2017, patients presenting for reproductive care at the University of Michigan were approached for study enrollment. Following consent, subjects completed detailed reproductive and health questionnaires.

Lack of trusted diagnostic tools for undetermined male infertility.

Semen analysis is the cornerstone of evaluating male infertility, but it is imperfect and insufficient to diagnose male infertility. As a result, about 20% of infertile males have undetermined infertility, a term encompassing male infertility with an unknown underlying cause. Undetermined male infertility includes two categories: (i) idiopathic male infertility-infertile males with abnormal semen analyses with an unknown cause for that abnormality and (ii) unexplained male infertility-males with "normal" semen analyses who are unable to impregnate due to unknown causes.

Male Infertility is a Women's Health Issue-Research and Clinical Evaluation of Male Infertility Is Needed.

Infertility is a devastating experience for both partners as they try to conceive. Historically, when a couple could not conceive, the woman has carried the stigma of infertility; however, men and women are just as likely to contribute to the couple's infertility. With the development of assisted reproductive technology (ART), the treatment burden for male and unexplained infertility has fallen mainly on women.

Histone modification signatures in human sperm distinguish clinical abnormalities.

Purpose: Alternations to the paternal epigenome, specifically the components of sperm chromatin, can lead to infertility in humans and potentially transmit aberrant information to the embryo. One key component of sperm chromatin is the post-translational modification of histones (PTMs). We previously identified a comprehensive profile of histone PTMs in normozoospermic sperm; however, only specific histone PTMs have been identified in abnormal sperm by antibody-based approaches and comprehensive changes to histone PTM profiles remain unknown.

Medical and elective fertility preservation: impact of removal of the experimental label from oocyte cryopreservation.

Purpose: The purpose of this study was to compare baseline characteristics and ovarian stimulation outcomes between patients presenting for medically indicated vs. elective fertility preservation consultation and to determine the impact of the 2013 ASRM guidelines on oocyte cryopreservation on the patient population presenting for fertility preservation consultation.

Methods: Retrospective cohort study conducted at an academic center.