Good laboratory practice for PGT-M: Turkish Society of Reproductive Medicine guidelines.

This guideline was prepared by the Turkish Society of Reproductive Medicine to define the conditions and requirements for an outsourced preimplantation genetic testing (PGT) programme in line with the experience and needs of practitioners. This guideline is intended to be a reference document for assisted reproductive technology centres, genetic diagnosis centres, non-governmental organizations working on reproductive health, legal experts, consultants working on laboratory accreditation, academicians specializing in ethical issues, and policy makers. The Consortium aims to provide recommendations addressing the challenges of genetic testing, especially PGT for monogenic diseases (PGT-M) due to the high rate of consanguineous marriage in Turkey.

Exposure of antral follicles to medroxyprogesterone acetate during stimulation does not cause molecular perturbations in gonadotropin-responsiveness and steroidogenic function of granulosa cells in progestin-primed cycles.

Study Question: Does medroxyprogesterone acetate (MPA) exposure in progestin-primed ovarian stimulation (PPOS) cycles cause molecular perturbations in the steroidogenic function and gonadotropin responsiveness of the granulosa cells?

Summary Answer: PPOS cycles are identical to traditional GnRH antagonist cycles not only for clinical IVF characteristics but also for gonadotropin receptor expression, response to gonadotropins, and steroidogenic function at the molecular level.

What Is Known Already: PPOS is increasingly used as an alternative to GnRH antagonists due to the inhibitory effect of progesterone on LH release by reducing GnRH pulsatility at the hypothalamic level. Although a growing body of evidence from clinical studies did not indicate significant differences between PPOS and antagonist protocols for IVF cycle characteristics and obstetrical outcomes, it is still unknown whether exposure of the antral follicle cohort to progesterone or its synthetic derivatives during ovarian stimulation causes any subtle molecular aberrations in terms of steroidogenesis and gonadotropin responsiveness.

Patients with gynecological malignancies are similar to other IVF patients without cancer for clinical and molecular reproductive parameters and DNA damage response pattern.

This study intended to investigate if gynecological cancers compromise ovarian function and reduce the success of assisted reproduction techniques (ART). No clinical and molecular data together is available on this issue for gynecological or other organ cancers. Steroidogenic pathways and DNA damage response characteristics of the granulosa cells retrieved from the 39 gynecological cancer patients were analyzed together with their clinical ART characteristics in comparison to 31 control ART patients.

Fertility and anatomical outcomes following hysteroscopic adhesiolysis: An 11-year retrospective cohort study to validate a new classification system for intrauterine adhesions (Urman-Vitale Classification System).

Objective: To propose a new classification system (Urman-Vitale Classification System) for intrauterine adhesions (IUAs) and to evaluate anatomical and fertility outcomes after hysteroscopic adhesiolysis accordingly.

Methods: A retrospective analysis of consecutive patients treated over 11 years by a single operator in a tertiary care hospital. Women with sonographic suspicion of IUAs were scheduled for hysterosalpingography (HSG) and hysteroscopy for confirmation and treatment.

The effect of earthquake experience on pregnancy outcomes: A systematic review and meta-analysis.

Objectives: Pregnant women are vulnerable to the health consequences of earthquakes, experiencing stress and limited access to healthcare. Despite the widespread impact of these events, knowledge about their effects on pregnancy outcomes is scarce and inconsistent. This systematic review and meta-analysis aimed to evaluate the available evidence, estimate the overall effect, and identify key research gaps about earthquake on pregnant women.

Progesterone signaling in the regulation of luteal steroidogenesis.

The corpus luteum is the major source of progesterone, the essential hormone for female reproductive function. While progesterone activity has been the subject of extensive research for decades, characterization of non-canonical progesterone receptor/signaling pathways provided a new perspective for understanding the complex signal transduction mechanisms exploited by the progesterone hormone. Deciphering these mechanisms has significant implications in the management of luteal phase disorders and early pregnancy complications.

Autophagy regulates sex steroid hormone synthesis through lysosomal degradation of lipid droplets in human ovary and testis.

Autophagy is an evolutionarily conserved process that aims to maintain the energy homeostasis of the cell by recycling long-lived proteins and organelles. Previous studies documented the role of autophagy in sex steroid hormone biosynthesis in different animal models and human testis. Here we demonstrate in this study that sex steroid hormones estrogen and progesterone are produced through the same autophagy-mediated mechanism in the human ovary in addition to the human testis.

IVF characteristics and the molecular luteal features of random start IVF cycles are not different from conventional cycles in cancer patients.

Study Question: Are the IVF parameters and the steroidogenic luteal characteristics of random-start IVF cycles different from conventional cycles in cancer patients?

Summary Answer: No; controlled ovarian stimulation cycles randomly started at late follicular phase (LFP) and luteal phase (LP) are totally comparable to those conventional IVF cycles started at early follicular phase (EFP) in terms of the expression of the enzymes involved in cholesterol utilization and steroid hormone biosynthesis pathways, gonadotropin receptor expression and, estradiol (E2) and progesterone (P4) production in addition to the similarities in ovarian response to gonadotropin stimulation, oocyte yield, fertilization rate and embryo development competency in cancer patients.

What Is Known Already: Random start ovarian stimulation protocols are commonly employed for oocyte and embryo freezing for fertility preservation in cancer patients with time constraints who do not have sufficient time to undergo ovarian stimulation initiated conventionally at EFP of the next cycle. No data is available regarding the molecular steroidogenic features of these cycles analyzed together with the clinical IVF characteristics in cancer patients.

Does Oocyte Retrieval Performance in Mono-follicular Cycles Differ by Physician Experience?

Oocyte pick-up (OPU) is considered as a minor surgical procedure and complications are very rare when performed by trained physicians. However, data on training standards are limited and assessment of proficiency is challenging. The aim of this study was to show the impact of physician experience on OPU performance in mono-follicular in vitro fertilization (IVF) cycles, using two measurable outcome parameters: successful oocyte retrieval and operative time.

Cholesterol uptake or trafficking, steroid biosynthesis, and gonadotropin responsiveness are defective in young poor responders.

Objective: To investigate whether poor ovarian response in young patients undergoing in vitro fertilization simply involves lesser follicle growth due to diminished ovarian reserve or whether there are intrinsic perturbations in the ovary.

Design: A translational research study.

Setting: University Hospital Translational Research Center.

Dynamic view of assisted reproduction in Turkey from 1996 to 2020.

Research Question: What are the trends and changes in patient demographics and practices in treatment with assisted reproductive technology (ART) in Turkey over 25 years?

Design: Data on patient demographics, cycle characteristics and clinical outcome of 29,541 cycles in 22,867 women who underwent treatment with ART between 1996 and 2020 were analysed according to calendar years. Regression and interrupted time series analysis were used to assess changes in patient characteristics, trends and effects of interventions on outcome.

Results: From 1996 to 2020, the average age of women undergoing treatment with ART increased from 32.

What is the optimum number of follicular flushes in mono-follicular in-vitro fertilization cycles in a poor responder population?

Objective: Assessment of the optimal number of follicular flushes on retrieval rate and quality of oocytes in mono-follicular in-vitro fertilization (IVF) cycles.

Material And Methods: A retrospective analysis of 246 oocyte pick-up procedures in mono-follicular IVF cycles of 226 poor responder women was performed. The primary endpoint was oocyte retrieval rate in the initial aspirate versus subsequent flushing episodes.

A Survey of Women Who Cryopreserved Oocytes for Non-medical Indications (Social Fertility Preservation).

To evaluate the expectations, experiences, and fertility awareness status of women who underwent social oocyte cryopreservation. Cohort survey study was conducted at an academic medical center. All women who underwent social oocyte cryopreservation between January 2015 and June 2016 were recruited.

The impact of dysmenorrhea and premenstrual syndrome on academic performance of college students, and their willingness to seek help.

Objective: To reveal the characteristics and prevalence of dysmenorrhea and Premenstrual syndrome (PMS) among college students and to investigate their impact on their academic performance.

Materials And Methods: This cross-sectional study was conducted between December 2017 and January 2018 at Koç University, Turkey. An online survey that included multiple-choice and short paragraph questions was prepared.

Terminal differentiation of human granulosa cells as luteinization is reversed by activin-A through silencing of Jnk pathway.

Molecular mechanisms underlying luteinization (terminal differentiation of granulosa and theca cells after ovulation) and luteolysis (demise of corpus luteum) are poorly understood in human ovary. Here we report that activin-A, after binding to its cognate receptors induces a functional luteolytic state and reverses luteinization phenotype by downregulating the expression of the steroidogenic enzymes, LH receptor and VEGF and reducing estradiol (E) progesterone (P) production and upregulating FSH receptor and cyclin D1 expression in human primary luteinized granulosa cells. Further, this action of activin-A involves downregulation of JNK signaling pathway and is opposite to that of human chorionic gonadotropin (hCG), which acts as a luteotropic hormone and improves luteal function through the activation of JNK pathway in the same cell type.

There is a cycle to cycle variation in ovarian response and pre-hCG serum progesterone level: an analysis of 244 consecutive IVF cycles.

We aimed to answer one key question, that was not previously addressed as to whether serum progesterone (P day) and its co-variates (estradiol (E) and the number of retrieved oocytes) of a given cycle can be predictive of the subsequent cycle when both cycles are consecutive and comparable for the stimulation protocol, gonadotropin dose and duration of stimulation. We analyzed such 244 consecutive (< 6 months) IVF cycles in 122 patients with GnRH agonist long protocol and found that P, E and the number of retrieved oocytes significantly vary between the two cycles. Although P increased (ranging from 4.

Anogenital distance in newborn infants conceived by assisted reproduction and natural conception.

Research Question: Does anogenital distance (AGD) differ in newborn infants conceived through assisted reproduction technology (ART) compared with those conceived naturally?

Design: This case-control study looked at anthropometric and anogenital measurements in 247 male and 200 female newborns born after ART (n = 121) or natural conception (n = 326), within 24 h of birth. Anogenital measurements included distance from the centre of the anus to the anterior clitoris (AGDAC) and to the posterior fourchette (AGDAF) in female infants, and from the centre of the anus to the posterior base of the scrotum (AGDAS) and to the anterior base of the penis (AGDAP) in male infants.

Results: ART mothers were older, more likely to be nulliparous and delivered by Caesarean section at an earlier gestational week.

hCG Improves Luteal Function and Promotes Progesterone Output through the Activation of JNK Pathway in the Luteal Granulosa Cells of the Stimulated IVF Cycles†.

Unlabelled: Human chorionic gonadotropin (hCG) is a luteotropic hormone that promotes the survival and steroidogenic activity of corpus luteum (CL) by acting through luteinizing hormone receptors (LHRs) expressed on luteinized theca and granulosa cells (GCs). Therefore, it is used to support luteal phase in in vitro fertilization (IVF) cycles to improve clinical pregnancy rates and prevent miscarriage. However, the molecular mechanism underlying this action of hCG is not well characterized.

Intrauterine administration of peripheral mononuclear cells in recurrent implantation failure: a systematic review and meta-analysis.

It has been proposed that intrauterine administration of peripheral blood mononuclear cells (PBMCs) modulates maternal immune response through a cascade of cytokines, chemokines and growth factors to favor implantation. We conducted a meta-analysis to verify the effect of intrauterine PBMC administration on the outcome of embryo transfer in women with recurrent implantation failure (RIF). All relevant trials published in PubMed, Web of Science and Cochrane library databases were searched.

Awareness of fertility and reproductive aging in women seeking oocyte cryopreservation, reproductive aged controls, and female health care professionals: A comparative study.

Objective: To compare the awareness of fertility and reproductive aging in women seeking oocyte cryopreservation (OC) with age matched controls.

Study Design: In this cross-sectional comparative study, women who were candidates for OC due to impending oocyte depletion (n = 81) were compared to age matched reproductive aged women (RAW) (n = 91) and female healthcare professionals (FHP) (n = 82) in terms of awareness about fertility and reproductive aging and knowledge about OC. A study specific 18-item questionnaire was constructed on the basis of previous research on OC and fertility.

High responders are not exempt from detrimental effects of prematurely rising progesterone levels in fresh embryo transfer cycles.

Research Question: Are high-responder IVF patients protected from the deleterious effect of prematurely elevated serum progesterone level on the probability of pregnancy?

Design: In this retrospective cohort study, 2971 autologous fresh embryo transfer IVF cycles with gonadotrophin-releasing hormone agonist long protocol were analysed to investigate whether the detrimental effect of prematurely rising progesterone levels on clinical pregnancy rate (CPR) varies depending on the magnitude of ovarian response. Nine different evenly spaced intervals were constructed for serum progesterone level on the human chorionic gonadotrophin day (<0.5/0.

Luteal granulosa cells from natural cycles are more capable of maintaining their viability, steroidogenic activity and LH receptor expression than those of stimulated IVF cycles.

Study Question: Are there any differences in the molecular characteristics of the luteal granulosa cells (GC) obtained from stimulated versus non-stimulated (natural) IVF cycles that may help explain the defective luteal phase in the former?

Summary Answer: Luteal GC of stimulated IVF cycles, particularly those of agonist-triggered antagonist cycles, are less viable ex vivo, express LH receptor and anti-apoptotic genes at lower levels, undergo apoptosis earlier and fail to maintain their estradiol (E2) and progesterone (P4) production in comparison to natural cycle GC.

What Is Known Already: Luteal function is defective in stimulated IVF cycles, which necessitates P4 and/or hCG administration (known as luteal phase support) in order to improve clinical pregnancy rates and prevent miscarriage. The luteal phase becomes shorter and menstruation begins earlier than a natural cycle if a pregnancy cannot be achieved, indicative of early demise of corpus luteum (premature luteolysis).

Bologna criteria are predictive for ovarian response and live birth in subsequent ovarian stimulation cycles.

Purpose: The ESHRE Working Group on Poor Ovarian Response defined a set of variables to define poor responders, named as the Bologna Criteria, but several concerns have been raised regarding their applicability and prognostic significance. In order to evaluate the clinical relevance of the criteria, we retrospectively analyzed the ovarian response and live birth rates in women who had consecutive IVF attempts, according to their fulfillment of the criteria.

Methods: The study group comprised 1153 and 288 women who had two and three consecutive ovarian stimulation (OS) cycles between May 2010 and January 2017, respectively.

Endogenous c-Jun N-terminal kinase (JNK) activity marks the boundary between normal and malignant granulosa cells.

Granulosa cell tumor of the ovary (GCT) is a very rare tumor, accounting for only 2% of all ovarian tumors. It originates from sex cords in the ovary and can be divided into adult (95%) and juvenile (5%) types based on histologic findings. To date, no clear etiologic process has been identified other than a missense point mutation in the FOXL2 gene.

Utilization of the Bologna criteria: a promise unfulfilled? A review of published and unpublished/ongoing trials.

Objective: To study the use of the Bologna criteria (BC) for the definition of poor ovarian responders (POR) in clinical practice and research.

Design: Systematic review of published and unpublished/ongoing trials between January 2012 and August 2017 on POR.

Setting: Not applicable.