The 50 most-cited articles in Fertility and Sterility, 2024

STUDY QUESTION: How should premature/primary ovarian insufficiency (POI) be diagnosed and managed, based on the best available evidence from published literature? SUMMARY ANSWER: The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae and treatment of POI. WHAT IS KNOWN ALREADY: Premature ovarian insufficiency (POI) presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life; fertility; and bone, cardiovascular and cognitive health. Although hormone therapy (HT) can mitigate some of these effects, many questions still remain regarding the optimal management of POI. STUDY DESIGN, SIZE, DURATION: , 2024, and written in English were included in the guideline. An integrity review was conducted for the randomised controlled trials (RCTs) on POI included in the guideline. PARTICIPANTS/MATERIALS, SETTING, METHODS: Based on the collected evidence, recommendations were formulated and discussed within the guideline development…

Uterine fibroids (UFs) are the most common female benign pelvic tumors, affecting >60% of patients aged 30-44 years. Uterine fibroids are asymptomatic in a large percentage of cases and may be identified incidentally using a transvaginal ultrasound or a magnetic resonance imaging scan. However, in approximately 30% of cases, UFs affect the quality of life and women's health, with abnormal uterine bleeding and heavy menstrual bleeding being the most common complaints, along with iron deficiency (ID) and ID anemia. Medical treatments used for UFs-related abnormal uterine bleeding include symptomatic agents, such as nonsteroidal antiinflammatory drugs and tranexamic acid, and hormonal therapies, including combined oral contraceptives, gonadotropin-releasing hormone agonists or antagonists, levonorgestrel intrauterine systems, selective progesterone receptor modulators, and aromatase inhibitors. Nevertheless, few drugs are approved specifically for UF treatment, and most of them manage the symptoms. Surgical options include fertility-sparing treatments, such as myomectomy, or…

OBJECTIVE: To report utilization, effectiveness, and safety of assisted reproductive technologies in 2015 and 2016. DESIGN: A retrospective, cross-sectional survey of 3,103 assisted reproductive technology clinics in 74 countries in 2015 and 3,249 clinics in 79 countries in 2016 that submitted cycle and pregnancy outcome data through national and regional registries. SETTING: Seventy-nine countries and >3,000 assisted reproductive technology clinics. PATIENT(S): Patients undergoing assisted reproductive technology procedures. INTERVENTION(S): Assisted reproductive technology. MAIN OUTCOME MEASURE(S): Outcomes on country, regional, and global levels. RESULT(S): Reported for 2015: 2,358,239 cycles with 548,652 infants born; for 2016: 2,807,963 cycles with 647,188 infants born. Estimated in 2015, ≥2,683,677 cycles resulted in >675,134 infants; in 2016, ≥3,100,448 cycles resulted in ≥723,026 infants. Reported cycles represent approximately 80% of global utilization. In 2015 and 2016, 27.6% and 27.8%, respectively, of women undergoing fresh autologous treatment cycles were aged ≥40…

The last few decades have witnessed a rise in the global uptake of in vitro fertilization (IVF) treatment. To ensure optimal use of this technology, it is important for patients and clinicians to have access to tools that can provide accurate estimates of treatment success and understand the contribution of key clinical and laboratory parameters that influence the chance of conception after IVF treatment. The focus of this review was to identify key predictors of IVF treatment success and assess their impact in terms of live birth rates. We have identified 11 predictors that consistently feature in currently available prediction models, including age, duration of infertility, ethnicity, body mass index, antral follicle count, previous pregnancy history, cause of infertility, sperm parameters, number of oocytes collected, morphology of transferred embryos, and day of embryo transfer.

Importance As part of the 2023 international evidence-based polycystic ovary syndrome (PCOS) guideline, this meta-analysis investigated the inclusion of Anti-Müllerian hormone (AMH) levels in the diagnostic criteria for PCOS. Objective To answer the following three questions: 1) Are AMH levels effective in diagnosing PCOS in adult women? 2) Are AMH levels effective in diagnosing PCOS in adolescents? Are AMH levels effective in diagnosing polycystic ovarian morphology (PCOM)? Data Sources Searches were conducted in six databases until July 31, 2023. Study Selection and Synthesis Eligible studies were those conducted in humans, published in English, and reporting sensitivity, specificity, and/or area under the curve values. Extracted data included study population, age, body mass index, AMH assay, cut-off value of AMH levels, sensitivity, specificity, and area under the curve values. The risk of bias was assessed using the quality assessment of diagnostic accuracy studies tool. A random effects model was used to test diagnostic accuracy. Main Outcomes Pooled sensitivity and…

IMPORTANCE: The clinical management of women with diminished ovarian reserve (DOR) is a challenge in the field of medically assisted reproduction. Several therapeutic strategies have been proposed, but with mixed results, mainly because the definition of DOR used was inconsistent among trials. OBJECTIVE: To investigate adjuvant treatments and protocols involving only women with DOR according to POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) criteria. DATA SOURCES: We conducted a systematic search using the MEDLINE (PubMed), EMBASE, and ISI Web of Knowledge databases to identify relevant studies published up to June 2024.The review protocol was registered at http://www.crd.york.ac.uk/PROSPERO/ (registration number: CRD42022346117). STUDY SELECTION AND SYNTHESIS: After duplication removal, the titles and abstracts of 4,806 articles were scrutinized, and 124 full-text articles were assessed for eligibility. In total, 38 randomized controlled trials were included in the qualitative/quantitative analysis. The following interventions were evaluated:…

IMPORTANCE: Endometriosis is an inflammatory disease, with different forms of expression and a variety of complaints. An endometrioma, an ovarian cyst with endometrium-like lining, is one of the most common expressions of abdominal endometriosis. These endometriomas can, in addition to medical treatment, be treated surgically. After surgery, hormonal therapy is still frequently used for the treatment of endometriosis in general and prevention of recurrence of endometriomas specifically. However, not all women want or can receive postoperative hormonal treatment. It is important for this group to determine the risk of anatomical recurrence of ovarian endometrioma after surgery for an endometrioma. OBJECTIVE: To determine the recurrence rate for surgically treated endometrioma without postoperative hormonal treatment. DATA SOURCES: We performed a systematic literature review and meta-analyses, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. MEDLINE, Embase, and the Cochrane library were searched until May 2023. The literature search was…

The prediction of menopause and premature ovarian insufficiency (POI) involves understanding the factors that contribute to the timing of these events. Menopause is a natural biological process marked by the cessation of menstrual periods, typically occurring around the age of 51. On the other hand, POI refers to the loss of ovarian function before the age of 40. Several factors have been used to predict menopause and POI such as age, antimüllerian hormone, inhibins and follicle-stimulating hormone serum levels, antral follicle counts, menstrual cycle length, and, recently, some genetic markers. It seems that age has the best predictive power and all the other ones are only adding in a very limited way to the prediction of menopause. Low levels of antimüllerian hormone in young women might indicate a greater risk for POI and could facilitate early diagnosis. It is, however, important to note that predicting the exact timing of menopause and POI is challenging, and individual variations are significant. Although these factors can provide some insights, they are not foolproof…

Objective To evaluate the association between sleep quality and ovarian reserve among women of reproductive age. Design Cross-sectional study. Subjects A total of 1,070 female participants aged 20–40 years enrolled from February 2023 to January 2024. Exposure Not applicable. Main Outcome Measures A questionnaire was administered to the participants to collect baseline information related to reproductive and lifestyle factors. Pittsburgh Sleep Quality Index (PSQI) was used to measure sleep quality. The assessment was conducted on ovarian reserve, including total antral follicle count (AFC), antimüllerian hormone (AMH) level, and basal sex hormone level. Results The study sample of 1,070 women had a mean age of 31.67 ± 4.41 years. A total of 314 participants (29.35%) were classified under the poor sleep group (PSQI score >5). Significant differences were observed in the follicle-stimulating hormone (FSH), luteinizing hormone, estradiol, testosterone, AFC, and AMH between the two groups. The poor sleep group exhibited significantly lower levels of AMH and AFC. The FSH levels in the…

OBJECTIVE: To explore factors influencing microdissection testicular sperm extraction (micro-TESE) success in hypogonadal men with nonobstructive azoospermia (NOA). DESIGN: A cohort study. SETTING: University-affiliated male reproductive health center. PATIENT(S): A total of 616 consecutive patients with NOA and hypogonadism (total testosterone [T] levels <350 ng/dL) underwent micro-TESE between 2014 and 2021. All patients had no prior sperm retrieval (SR) history. INTERVENTION(S): Patients aged 23-55 years underwent comprehensive clinical, laboratory, and histopathological diagnostic evaluation for NOA and were further categorized into two cohorts on the basis of pre-SR hormonal stimulation. MAIN OUTCOME MEASURE(S): A multivariable logistic regression analysis explored the associations between patient variables and micro-TESE success, defined as the presence of viable spermatozoa in extracted specimens. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were computed to assess the relationship between SR success and relevant predictors. Sperm retrieval rates were…

Fibroids significantly impact the quality of life (QOL) and mental health of affected women. However, there are limited comparative data on QOL measures after medical, surgical, and radiologic interventions in women with fibroids. This study aimed to assess the current literature evaluating the impact of fibroids on QOL measures using several validated questionnaires for radiologic, medical, or surgical interventions or a combination of interventions before and after treatment. PubMed, PsycINFO, ClinicalTrials.gov, Embase, and Cochrane Library were searched from January 1990 to October 2023 to evaluate the available evidence, and the risk of bias was assessed using Cochrane RoB 2.0 or the Newcastle-Ottawa Scale. The review criteria included randomized controlled trials (RCTs) and observational cohort studies that included premenopausal women with symptomatic uterine fibroids, confirmed by imaging, who underwent an intervention to target fibroid disease. Only reports using validated questionnaires with a numerical baseline (pretreatment) and posttreatment scores were included. The…

OBJECTIVE: To study the cumulative live birth rate (CLBR) after the first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment in women with or without deep-infiltrating endometriosis (DIE) and/or endometrioma diagnosed by transvaginal ultrasonography (TVUS), using the International Deep Endometriosis Analysis (IDEA) group definitions. DESIGN: Prospective observational cohort study at a university hospital. PATIENTS(S): In total, 1,040 women with subfertility aged 25 to ≤39 years were undergoing their first IVF/ICSI treatment between January 2019 and October 2022. Of these, 234 (22.5%; 95% confidence interval [CI], 20.0-25.0) women were diagnosed with DIE and/or endometrioma at systematic TVUS before starting their treatment. INTERVENTION(S): All women underwent their first IVF or ICSI treatment. Fresh and/or frozen embryos from the first cycle were used until pregnancy was achieved or no embryos remained. MAIN OUTCOME MEASURE(S): Cumulative live birth rate after the first IVF/ICSI cycle in women with or without DIE and/or endometrioma. RESULT(S): The…

OBJECTIVE: To study educational gradients in births after medically assisted reproduction across 5 countries with different institutional arrangements. DESIGN: We use logistic regression and compute predicted probabilities to estimate the association between education and giving birth after assisted reproduction, before and after adjustment for maternal age at delivery and marital/partnership status, using an overall sample of about 3.9 million live births in 5 countries. SETTINGS: Not applicable. PATIENTS: This study includes survey or register data containing information on births in 5 countries: N = 61,564 for Denmark, N = 37,533 for France, N = 12,889 for Spain, N = 17,097 for the United Kingdom, and N = 3,700,442 for the United States. INTERVENTION (FOR RCT) OR EXPOSURE (FOR OBSERVATIONAL STUDIES): None. MAIN OUTCOME MEASURES: The probability of a child being born after medically assisted reproduction for mothers with a university degree relative to those having less than a university degree. RESULTS: University-educated mothers are more likely to give birth after assisted…

Linear mixed models are regularly used within the field of reproductive medicine. This manuscript explains the basics of mixed models, when they could be used, and how they could be applied.

OBJECTIVE: To assess whether the use of assisted reproductive technology (ART) therapy for conception is associated with imprinting disorders in children and the impact of parental factors related to infertility. DESIGN: A nationwide register-based cohort study. SETTING: Swedish national registers and nationwide quality IVF register. PATIENT(S): All liveborn singletons in Sweden (N = 2,084,127) between 1997 and 2017 with follow-up to December 31, 2018. INTERVENTION(S): The use of specific methods implemented in ART. MAIN OUTCOME MEASURE(S): The International Classification of Diseases version 10 was used to identify three distinct imprinting disorder groups: Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS), and Silver-Russell syndrome (SRS), as well as central precocious puberty. The Cox model combined with inverse probability treatment weights was used to estimate the weighted hazard ratio (wHR) with a 95% confidence interval (CI), accounting for multiple confounders. RESULT(S): A total of 1,044 children were diagnosed with the disorders of interest, and 52 of them…

OBJECTIVE: To undertake a one-stage meta-analysis of individual patient data from randomized trials comparing individualized dosing of follitropin delta vs. other forms of follitropin (alpha and beta) for live birth (LB) rates (LBR) and safety parameters in women undergoing ovarian stimulation for in vitro fertilization treatment. DESIGN: Systematic review with individual patient data meta-analysis. SETTING: Not applicable. PATIENTS: Women undergoing ovarian stimulation for in vitro fertilization treatment. INTERVENTIONS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Web of Science to identify eligible phase 3 trials between January 1, 2000, and February 1, 2023. MAIN OUTCOME MEASURES: All analyses were based on individual participant data. We used a general linear mixed effects logistic regression model using fixed effects for treatment drugs interacting with log (AMH) level, age, and random effects for country and trial to compare the primary efficacy and safety outcomes of LB and early ovarian hyperstimulation syndrome (OHSS) and/or the…

OBJECTIVE: To study the fertility outcomes of women who tried to conceive after breast cancer (BC) treatment and fertility preservation. DESIGN: Retrospective observational, bicentric cohort study. SETTING: University hospital. PATIENTS: Patients with BC. INTERVENTION: All patients who had undergone fertility preservation before BC treatment between January 2013 and July 2019 were included (n = 844). The endpoint date was March 1, 2022. Patients with missing data on pregnancy attempts after a cancer diagnosis (n = 195) were excluded from the pregnancy analysis. MAIN OUTCOME MEASURES: Cumulative incidences of pregnancy and live birth (LB) were calculated. For women who became pregnant, the time to conception was calculated between the first fertility preservation consultation and the estimated day of conception. For those who did not conceive, we considered the time between the first fertility preservation consultation and the endpoint date, or the date of patient death. A Cox regression model was used to study the predictive factors for pregnancy and LB. RESULTS: Among the 649…

OBJECTIVE: The World Endometriosis Research Foundation established the Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) to create standardized documentation tools (with common data elements) to facilitate the comparison and combination of data across different research sites and studies. In 2014, 4 data research standards were published: clinician-reported surgical data, patient-reported clinical data, and fluid and tissue biospecimen collection. Our current objective is to create an EPHect standard for the clinician-reported physical examination (EPHect-PE) for research studies. DESIGN: An international consortium involving 26 clinical and academic experts and patient partners from 11 countries representing 25 institutions and organizations. Two virtual workshops, followed by the development of the physical examination standards underwent multiple rounds of iterations and revisions. SUBJECTS: N/A MAIN OUTCOME MEASURE(S): N/A RESULT(S): The EPHect-PE tool provides standardized assessment of physical examination characteristics and pain phenotyping. Data elements…

OBJECTIVE: To explore whether intracytoplasmic sperm injection (ICSI) would increase the malformation risk in fetuses and live births compared with conventional in vitro fertilization (IVF). DESIGN: Retrospective cohort study. PATIENT(S): Data were collected from couples who underwent conventional IVF or ICSI from January 2009 to December 2019 at the Center for Reproductive Medicine of Peking University Third Hospital in the People's Republic of China. A total of 46,167 conventional IVF fresh transfer cycles and 33,247 ICSI fresh transfer cycles were included. INTERVENTION(S): Intracytoplasmic sperm injection and conventional IVF. MAIN OUTCOME MEASURE(S): The primary outcomes were congenital abnormalities in live births. The secondary outcomes included the pregnancy outcomes, the malformations among the miscarriages, specific types of malformations in live births, birth weight, and sex. RESULT(S): The rates of congenital malformations in conventional IVF and ICSI were 5.44‰ and 5.78‰, respectively. There was no statistically significant difference between the two groups, as…

OBJECTIVE: To study the specific mechanisms through which progesterone and selective progesterone receptor modulators impact the growth, synthesis, and accumulation of the extracellular matrix in uterine leiomyomas. DESIGN: Laboratory study. SETTING: Academic Research Institutions. PATIENTS (S): This study involved reproductive-age women diagnosed with infertility associated uterine leiomyomas who underwent myomectomy either after selective progesterone receptor modulator ulipristal acetate (UA) treatment or without any pharmacological pretreatment. Control samples included healthy myometrium tissue (n = 100). Specimens were obtained from the Department of Reproduction and Gynecological Endocrinology and Biobank, Medical University of Bialystok, Poland. INTERVENTIONS: Daily (5 mg/d) UA treated for 2 months (n = 100) and untreated (n = 150) patients with uterine leiomyomas or normal healthy myometrium (n = 100) tissue samples immediately after surgery were collected for transcriptional analysis and assessments. MAIN OUTCOME MEASURES: Progesterone-induced activation of the signaling…

OBJECTIVE: To evaluate the effect of relugolix combination therapy (relugolix CT; 40 mg relugolix, 1 mg estradiol, and 0.5 mg norethisterone acetate) for up to 2 years in the SPIRIT long-term extension study on functioning and health-related quality of life (QoL), using the Endometriosis Health Profile (EHP)-30 questionnaire, and assess how changes in QoL domains correlated with improvements in dysmenorrhea as well as nonmenstrual pelvic pain (NMPP). DESIGN: Long-term extension study of the SPIRIT phase 3 trials. SETTING: Clinics and University Hospitals. PATIENT(S): Premenopausal women with moderate-to-severe endometriosis pain who previously completed the randomized SPIRIT trials were eligible to enroll in an 80-week long-term extension where all women received relugolix CT. INTERVENTION(S): Relugolix CT (relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg). MAIN OUTCOME MEASURE(S): Least squares (LS) mean changes in the EHP-30 domain and total scores from baseline (pivotal) were analyzed using a mixed-effects model. Results up to 104 weeks are reported by a pivotal…

OBJECTIVE: To describe the prevalence of multimorbidity among individuals with primary ovarian insufficiency (POI) and early menopause compared with those with the average age of menopause. DESIGN: Prospective cohort. SUBJECTS: This prospective cohort encompassed female postmenopausal individuals from the Canadian Longitudinal Study on Aging. The Canadian Longitudinal Study on Aging collected cross-sectional data from 50,000 community-dwelling Canadians aged 45-85 years between 2010 and 2015. EXPOSURE: The primary exposure was POI (defined by onset of menopause at the age of <40 years). Comparators included average age of menopause (age, 46-55 years), early menopause (40-45 years), and late-onset menopause (56-65 years) and those who underwent hysterectomy. MAIN OUTCOME MEASURE(S): The primary outcome was multimorbidity, which was defined as two or more chronic conditions. The secondary outcomes were severe multimorbidity (defined as 3 or more chronic conditions) and frequencies of specific chronic conditions among a comprehensive list of 15 individual conditions. We assessed the…