In vitro growth of secondary follicles from cryopreserved-thawed ovarian cortex.

Study Question: Can secondary follicles be obtained from cultured cryopreserved-thawed human ovarian cortical tissue?

Summary Answer: We obtained high-quality secondary follicles from cultured cryopreserved-thawed human ovarian cortical tissue from cis female donors (cOVA), but not from trans masculine donors (tOVA) in the same culture conditions.

What Is Known Already: The in vitro growth of oocytes present in unilaminar follicles into metaphase II stage (MII) oocytes has been previously achieved starting from freshly obtained ovarian cortical tissue from adult cis female donors. This involved a multi-step culture protocol and the first step included the transition from unilaminar follicles to multilayered secondary follicles.

Classification of Atretic Small Antral Follicles in the Human Ovary.

The reproductive lifespan in humans is regulated by a delicate cyclical balance between follicular recruitment and atresia in the ovary. The majority of the small antral follicles present in the ovary are progressively lost through atresia without reaching dominance, but this process remains largely underexplored. In our study, we investigated the characteristics of atretic small antral follicles and proposed a classification system based on molecular changes observed in granulosa cells, theca cells, and extracellular matrix deposition.

Dynamic culture of cryopreserved-thawed human ovarian cortical tissue using a microfluidics platform does not improve early folliculogenesis.

Current strategies for fertility preservation include the cryopreservation of embryos, mature oocytes or ovarian cortical tissue for autologous transplantation. However, not all patients that could benefit from fertility preservation can use the currently available technology. In this regard, obtaining functional mature oocytes from ovarian cortical tissue would represent a major breakthrough in fertility preservation as well as in human medically assisted reproduction.

Single-Cell Transcriptomics Analysis of Human Small Antral Follicles.

Human ovarian folliculogenesis is a highly regulated and complex process. Characterization of follicular cell signatures during this dynamic process is important to understand follicle fate (to grow, become dominant, or undergo atresia). The transcriptional signature of human oocytes and granulosa cells (GCs) in early-growing and ovulatory follicles have been previously described; however, that of oocytes with surrounding GCs in small antral follicles have not been studied yet.

Long-Term Risk of Ovarian Cancer and Borderline Tumors After Assisted Reproductive Technology.

Background: Long-term effects of assisted reproductive technology (ART) on ovarian tumor risk are unknown.

Methods: This nationwide cohort study comprises 30 625 women who received ovarian stimulation for ART in 1983-2000 and 9988 subfertile women not treated with ART. Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry until July 2018.

Previous caesarean section is associated with lower subsequent in vitro fertilization live birth rates.

This retrospective cohort study examines the association between previous mode of delivery and subsequent live birth rate in women who become pregnant after in vitro fertilization (IVF) or intra cytoplasmic sperm injection (ICSI) after their first delivery. The study included 112 women with a previous caesarean section and 418 women with a previous vaginal delivery, and a total of 1588 embryo transfers between January 2005 and June 2016 (Leiden University Medical Centre, the Netherlands). The mean age was 35 years and mean number of embryos transferred per attempt, 1.

Ovarian tissue cryopreservation: Low usage rates and high live-birth rate after transplantation.

Introduction: The likelihood of survival after cancer treatment among young women with cancer has increased considerably, quality of life after treatment has drawn more attention. However, in young fertile women, fertility preservation is an important issue with regard to quality of life. One of the options of fertility preservation is ovarian tissue cryopreservation.

At Term, XmO and XpO Mouse Placentas Show Differences in Glucose Metabolism in the Trophectoderm-Derived Outer Zone.

Genetic mouse model (39,XO) for human Turner Syndrome (45,XO) harboring either a single maternally inherited (Xm) or paternally inherited (Xp) chromosome show a pronounced difference in survival rate at term. However, a detailed comparison of XmO and XpO placentas to explain this difference is lacking. We aimed to investigate the morphological and molecular differences between XmO and XpO term mouse placentas.

Human Extravillous Trophoblasts Penetrate Decidual Veins and Lymphatics before Remodeling Spiral Arteries during Early Pregnancy.

In humans, the defective invasion of the maternal endometrium by fetal extravillous trophoblasts (EVTs) can lead to insufficient perfusion of the placenta, resulting in pregnancy complications that can put both mother and baby at risk. To study the invasion of maternal endometrium between (W)5.5-12 weeks of gestation by EVTs, we combined fluorescence in situ hybridization, immunofluorescence and immunohistochemistry to determine the presence of (male) EVTs in the vasculature of the maternal decidua.

Ovarian Stimulation for In Vitro Fertilization and Long-term Risk of Breast Cancer.

Importance: Previous studies of breast cancer risk after in vitro fertilization (IVF) treatment were inconclusive due to limited follow-up.

Objective: To assess long-term risk of breast cancer after ovarian stimulation for IVF.

Design, Setting, And Participants: Historical cohort (OMEGA study) with complete follow-up through December 2013 for 96% of the cohort.

On the development of extragonadal and gonadal human germ cells.

Human germ cells originate in an extragonadal location and have to migrate to colonize the gonadal primordia at around seven weeks of gestation (W7, or five weeks post conception). Many germ cells are lost along the way and should enter apoptosis, but some escape and can give rise to extragonadal germ cell tumors. Due to the common somatic origin of gonads and adrenal cortex, we investigated whether ectopic germ cells were present in the human adrenals.

Stronger T-Cell Alloreactivity and Diminished Suppressive Capacity of Peripheral Regulatory T Cells in Infertile Women Undergoing In Vitro Fertilization.

Problem: Increasing evidence suggests modulation of the maternal immune response to be essential for successful pregnancy. We studied the immunophenotypic profile and function of peripheral blood T lymphocytes in infertile women undergoing in vitro fertilization (IVF) and fertile control population.

Method: We collected peripheral blood mononuclear cells (PBMC) from infertile patients with recurrent implantation failure (RIF), infertile patients with successful IVF (IVFs), and normal fertile women.

Piwi proteins and piRNAs in mammalian oocytes and early embryos.

Germ cells of most animals critically depend on piRNAs and Piwi proteins. Surprisingly, piRNAs in mouse oocytes are relatively rare and dispensable. We present compelling evidence for strong Piwi and piRNA expression in oocytes of other mammals.

Development of the follicular basement membrane during human gametogenesis and early folliculogenesis.

Background: In society, there is a clear need to improve the success rate of techniques to restore fertility. Therefore a deeper knowledge of the dynamics of the complex molecular environment that regulates human gametogenesis and (early) folliculogenesis in vivo is necessary. Here, we have studied these processes focusing on the formation of the follicular basement membrane (BM) in vivo.

Perinatal outcome, health, growth, and medical care utilization of 5- to 8-year-old intracytoplasmic sperm injection singletons.

Objective: To evaluate short- and long-term health in intracytoplasmic sperm injection (ICSI) singletons.

Design: Follow-up study.

Setting: University medical center, assessments between March 2004 and May 2005.

Cognitive development of singletons born after intracytoplasmic sperm injection compared with in vitro fertilization and natural conception.

Objective: To investigate cognitive development of singletons conceived by intracytoplasmic sperm injection (ICSI) at 5-8 years of age.

Design: Follow-up study.

Setting: University medical center, assessments between March 2004 and May 2005.

Matched follow-up study of 5-8 year old ICSI-singletons: comparison of their neuromotor development to IVF and naturally conceived singletons.

Background: Intracytoplasmic sperm injection (ICSI) is an invasive technique of artificial reproduction. We investigated the effect of ICSI on neuromotor development in 5-8 year old singletons.

Methods: We did a follow-up of ICSI-singletons born between 1996 and 1999 after treatment in the Leiden University Medical Center and compared them with matched controls born after in vitro fertilization (IVF) and natural conception (NC).