The 50 most-cited articles in Fertility and Sterility, 2023

STUDY QUESTION: What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? SUMMARY ANSWER: International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS. WHAT IS KNOWN ALREADY: The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met,…

We performed a comprehensive narrative synthesis of systematic reviews with meta-analysis published in the last 5 years on the association of endometriosis and adenomyosis with reproductive and obstetric outcomes. This review aimed to define the information on which to base preconceptional counseling and clarify whether and in which cases pregnant women with endometriosis and adenomyosis should be referred to tertiary care centers and followed as high-risk obstetric patients. Reduced pregnancy and live birth rates and an increased miscarriage rate were observed in women with endometriosis and adenomyosis. The effect was larger in women with adenomyosis than in those with endometriosis. Women with superficial peritoneal and ovarian endometriosis do not appear to be at considerably increased risk of major obstetric and neonatal complications, whereas women with severe endometriosis, whether operated or not, are at several-fold increased risk of placenta previa. Moreover, deep infiltrating endometriosis is a risk factor for spontaneous hemoperitoneum in pregnancy and is associated with…

Endometriosis and adenomyosis are closely related disorders. Their pathophysiologies are extremely similar. Both tissues originate from the eutopically located intracavitary endometrium. Oligoclones of endometrial glandular epithelial cells with somatic mutations and attached stromal cells may give rise to endometriosis if they travel to peritoneal surfaces or the ovary via retrograde menstruation and/or may be entrapped in the myometrium to give rise to adenomyosis. In both instances, the endometrial cell populations possess survival and growth capabilities conferred by somatic epithelial mutations and epigenetic abnormalities in stromal cells. Activating mutations of KRAS are the most commonly found genetic variant in endometriotic epithelial cells, whereas the adenomyotic epithelial cells almost exclusively bear KRAS mutations. Epigenetic abnormalities in the stromal cells of endometriosis and adenomyosis are very similar and involve an abnormal expression pattern of nuclear receptors, including the steroid receptors. These epigenetic defects give rise to excessive local estrogen…

Worldwide, more than 10 million children have been born after assisted reproduction technology (ART), comprising up to 7.9% of children born in Europe and up to 5.1 % of children born in the US in 2018. The short-term outcome for children born after ART is well-known from numerous publications, with higher rates of preterm birth and low birth weight in children born after fresh embryo transfer and higher rates of large for gestational age and high birth weight in children born after frozen embryo transfer compared with children born after spontaneous conception. Higher rates of birth defects in children born after ART have also been shown consistently over time. Studies on long-term health outcomes after ART are scarcer but suggest an increased risk of altered blood pressure and cardiovascular function in children born after ART. In this review, we summarize long-term health outcomes in children born after ART and discuss whether the increased health risks are associated with intrinsic maternal or paternal factors related to subfertility or ART treatments per se. Finally, we…

IMPORTANCE: To date, recurrent implantation failure (RIF) has no clear definition and no clearly identified impaired function. Hence, the term RIF is currently used somewhat haphazardly, on the basis of clinicians' judgment. OBJECTIVE: International experts in reproductive medicine met on July 1, 2022, in Lugano, Switzerland, to review the different facets of RIF and define the diagnosis and its appropriate management. EVIDENCE REVIEW: A systematic review without meta-analysis of studies published in English from January 2015 to May 2022. FINDINGS: Data indicated that RIF has been largely overevaluated, overdiagnosed, and overtreated without sufficient critical assessment of its true nature. Our analyses show that true RIF is extremely uncommon-occurring in <5% of couples with infertility-and that reassurance and continued conventional therapies are warranted in most cases of assisted reproductive technology (ART) failure. Although the true biologic determinants of RIF may exist in a small subset of people with infertility, they elude the currently available tools for assessment.…

Oocyte in vitro maturation (IVM) is an assisted reproductive technology with a long and sometimes checked history. It is a minimally invasive technique involving the deliberate collection of immature oocytes from patients that have received no or minimal ovarian stimulation and the culture of oocytes to maturity in vitro, before standard procedures thereafter. Now, IVM is classified as nonexperimental and is primarily indicated for patients with a high antral follicle count, especially patients with polycystic ovaries or polycystic ovary syndrome, as well as for fertility preservation in cancer patients. In the recent past, IVM practice has had a confusing array of clinical protocols and has been slow to adapt to new scientific insights; however, recently, significant advances have been made in IVM culture methods based on new knowledge from animal studies, combined with defining a simple patient treatment protocol. These improvements have led to significant recent progress in IVM practice to the extent that IVM is now routinely practiced in a growing number of centers with…

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that impacts women worldwide. There are several racial and ethnic differences in PCOS phenotypes and in PCOS- associated metabolic dysfunction. In this review, we summarize the current literature on disparities in the diagnosis and outcomes associated with PCOS in the United States. Future studies are needed to address gaps in knowledge for racial and ethnic-specific differences in PCOS, and include a large number of non-White and/or Hispanic participants in PCOS studies.

OBJECTIVE: To investigate the association between the number of oocytes retrieved and the numbers of fertilized oocytes and blastocysts and cumulative and primary transfer live birth rates (LBRs). DESIGN: Retrospective study. SETTING: Retrieval cycles and linked embryo transfers from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. PATIENT(S): Patients in the United States undergoing autologous in vitro fertilization cycles from 2014 to 2019 (n = 402,411 cycles). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Normally fertilized oocytes, blastocysts, and cumulative and primary transfer LBRs. RESULT(S): There was a strong positive linear correlation between oocytes and fertilized oocytes and between oocytes and blastocysts. The cumulative LBR increased rapidly with the number of oocytes retrieved to approximately 16-20 oocytes, at which point it continued to increase but with diminishing returns. The increasing trend of the cumulative LBR was observed when stratifying patients by age and antimüllerian hormone and after controlling for confounding…

OBJECTIVE: To compare the responses of the large language model-based "ChatGPT" to reputable sources when given fertility-related clinical prompts. DESIGN: The "Feb 13" version of ChatGPT by OpenAI was tested against established sources relating to patient-oriented clinical information: 17 "frequently asked questions (FAQs)" about infertility on the Centers for Disease Control (CDC) Website, 2 validated fertility knowledge surveys, the Cardiff Fertility Knowledge Scale and the Fertility and Infertility Treatment Knowledge Score, as well as the American Society for Reproductive Medicine committee opinion "optimizing natural fertility." SETTING: Academic medical center. PATIENT(S): Online AI Chatbot. INTERVENTION(S): Frequently asked questions, survey questions and rephrased summary statements were entered as prompts in the chatbot over a 1-week period in February 2023. MAIN OUTCOME MEASURE(S): For FAQs from CDC: words/response, sentiment analysis polarity and objectivity, total factual statements, rate of statements that were incorrect, referenced a source, or noted the value of…

OBJECTIVE: To explore the role of gut dysbiosis-derived β-glucuronidase (GUSB) in the development of endometriosis (EMs). DESIGN: 16S rRNA sequencing of stool samples from women with (n = 35) or without (n = 30) endometriosis and from a mouse model was conducted to assess gut microbiome changes and identify molecular factors influencing the development of endometriosis. Experiments in vivo in an endometriosis C57BL6 mouse model and in vitro verified the level of GUSB and its role in the development of EMs. SETTING: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University; Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases. PATIENT(S): Women of reproductive age with a histological diagnosis of endometriosis were enrolled in the endometriosis group (n = 35) and infertile or healthy age-matched women who had undergone a gynecological or radiological examination in the control group (n = 30). Fecal and blood samples were taken the day before surgery. Paraffin-embedded sections from 50 bowel endometriotic…

Approximately 80% of miscarriages happen within the first 12 weeks of gestation. More than half of early losses result from genetic defects, usually presenting as abnormal chromosome numbers or gene rearrangements in the embryo. However, the impact of genetics on pregnancy loss goes well beyond embryonic aneuploidy. For example, the use of big data has recently led to the discovery of specific gene mutations that may be implicated in sporadic and recurrent miscarriages. Further, emerging data suggest that genetic factors play a role in conditions for which there is a causative association with recurrent pregnancy loss. Here, we summarize the evidence on the genetics of miscarriage and provide an overview of the diagnosis and prevention of genetic causes associated with sporadic and recurrent pregnancy loss.

IMPORTANCE: Previous reviews have shown that a history of cesarean section (CS) is associated with a worse in vitro fertilization (IVF) prognosis. To date, whether the decline in the IVF chances of success should be attributed to the CS procedure itself or to the presence of isthmocele remains to be clarified. OBJECTIVE: To summarize the available evidence regarding the impact of isthmocele on IVF outcomes. DATA SOURCES: Electronic databases and clinical registers were searched until May 30, 2023. STUDY SELECTION AND SYNTHESIS: Observational studies were included if they assessed the effect of isthmocele on IVF outcomes. Comparators were women with isthmocele and women without isthmocele with a previous CS or vaginal delivery. Study quality was assessed using the modified Newcastle-Ottawa Scale. MAIN OUTCOMES: The primary outcome was the live birth rate (LBR). The effect measures were expressed as adjusted odds ratios (aORs) and unadjusted odds ratios (uORs) with 95% confidence intervals (95% CIs). The body of evidence was assessed using the Grading of Recommendations Assessment,…

Endometriosis is a disease marked by more than just pain and infertility, as it transcends the well-characterized physical symptoms to be frequently associated with mental health issues. This review focuses on the associations between endometriosis and anxiety, depression, sexual dysfunction, and eating disorders, all of which show a higher prevalence in women with the disease. Studies show that pain, especially the chronic pelvic pain of endometriosis, likely serves as a mediating factor. Recent studies evaluating genetic predispositions for endometriosis and mental health disorders suggest a shared genetic predisposition. Healthcare providers who treat women with endometriosis should be aware of these associations to best treat their patients. A holistic approach to care by gynecologists as well as mental health professionals should emphasize prompt diagnosis, targeted medical interventions, and psychological support, while also recognizing the role of supportive relationships in improving the patient's quality of life.

OBJECTIVE: To assess the cellular and molecular landscape of adenomyosis. DESIGN: Single-cell analysis of genome-wide messenger RNA (mRNA) expression (single-cell RNA sequencing) of matched tissues of endometrium, adenomyosis, and myometrium using relatively large numbers of viable cells. SETTING: Not applicable. PATIENT(S): Patients (n = 3, age range 40-44 years) undergoing hysterectomy for diffuse adenomyosis. MAIN OUTCOME MEASURE(S): Definition of the molecular landscape of matched adenomyotic, endometrial and myometrial tissues from the same uterus using single-cell RNA sequencing and comparison of distinct cell types in these tissues to identify disease-specific cell populations, abnormal gene expression and pathway activation, and mesenchymal-epithelial interactions. RESULT(S): The largest cell population in the endometrium was composed of closely clustered fibroblast groups, which comprise 36% of all cells and seem to originate from pericyte progenitors differentiating to estrogen/progesterone receptor-expressing endometrial stromal- cells. In contrast, the entire fibroblast…

OBJECTIVE: To evaluate which girls with Turner syndrome (TS) could benefit from fertility preservation by ovarian tissue cryopreservation on the basis of karyotype, puberty status, and hormonal data. DESIGN: Prospective intervention study; participants were included between 2018 and 2020. SETTING: Tertiary hospital in the Netherlands. PATIENTS: In total, 106 girls with TS aged between 2 and 18 years were included. Girls with minor X chromosome deletions, Y chromosomal content, active infections, or contraindications for surgery were excluded. INTERVENTION: A laparoscopic unilateral ovariectomy was performed to obtain ovarian cortical tissue for cryopreservation. One tissue fragment per participant was used to determine the number of follicles per ovary by serial sectioning and staining. Chromosome analysis was performed on lymphocytes and buccal cells. A blood sample was taken before the ovariectomy for hormonal analysis. MAIN OUTCOME MEASURES: The presence of follicles in ovarian cortex tissue from girls with TS in relation to karyotype, puberty status, and hormonal data. RESULTS:…

The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1. Our field should aggressively explore and implement courses of action to increase the number of qualified, highly trained REI physicians trained annually. We recommend efforts to increase the number of REI fellowships and the size complement of existing fellowships be prioritized where possible. These courses of action include: a. Increase the number of REI fellowship training programs. b. Increase the number of fellows trained at current REI fellowship programs. c. The pros and cons of a…