Primary Ovarian Insufficiency and Ovarian Aging.

Primary ovarian insufficiency (POI) is a complex condition of aberrant ovarian aging. POI etiologies are varied, and most cases have no identifiable underlying cause. Caring for women with POI requires an approach that understands the importance of ovarian function in a variety of target organs and tissues.

Meeting the demand for fertility services: the present and future of reproductive endocrinology and infertility in the United States.

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 2-year focused clinical fellowship track for fellows interested primarily in ART practice were extensively explored. We do not recommend shortening the REI fellowship to 2 years at this time, because efforts should be focused on increasing the number of fellowship training slots (1a and b). 2. It is recommended that the field aggressively implements courses of action to increase the number of and appropriate usage of non-REI providers to increase clinical efficiency under appropriate board-certified REI physician supervision. 3. Automating processes through technologic improvements can free providers at all levels to practice at the top of their license.

Primary ovarian insufficiency has strong familiality: results of a multigenerational genealogical study.

OBJECTIVE: To determine the familiality of primary ovarian insufficiency (POI) at population level through examination of multigenerational genealogical information linked to electronic medical records. DESIGN: Case-control study. SETTING: Not applicable. PATIENT(S): Women with POI were identified using International Classification of Disease 9 and 10 codes in electronic medical records (1995-2021) from 2 major health care systems in Utah and reviewed for accuracy. Cases were linked to genealogy information in the Utah Population Database (UPDB). All included POI cases (n = 396) were required to have genealogy information available for at least 3 generations of ancestors. The risk of POI in relatives was compared with population rates for POI matched by age, sex, and birthplace. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Relative risk of POI in first-, second-, and third-degree relatives. RESULT(S): We identified 396 validated cases of POI with an associated 2,132 first-degree relatives, 5,245 second-degree relatives, and 10,853 third-degree relatives. We found an increased risk of POI among the extended relatives of cases. Specifically, first-degree relatives demonstrated an 18-fold increased risk of POI compared with controls relative risk ([RR],18.52 95% confidence interval [CI], 10.12-31.07), second-degree relatives demonstrated a 4-fold increase (RR, 4.21; CI, 1.15-10.79), and third-degree relatives demonstrated a 2.7-fold increase (RR, 2.65; CI, 1.14-5.21]). CONCLUSION(S): This is the first population-based study to assess the familial clustering of POI. The data demonstrate excess familiality, familial clustering of POI in excess compared with matched population rates of disease, among first-, second-, and third-degree relatives. These findings support a genetic contribution to POI.

Semen parameter thresholds and time-to-conception in subfertile couples: how high is high enough?

STUDY QUESTION: What thresholds for total sperm count, sperm concentration, progressive motility, and total progressive motile sperm count (TPMC) are associated with earlier time-to-conception in couples undergoing fertility evaluation? SUMMARY ANSWER: Values well above the World Health Organization (WHO) references for total sperm count, concentration, and progressive motility, and values up to 100 million for TPMC were consistently associated with earlier time-to-conception and higher conception rates. WHAT IS KNOWN ALREADY: Although individual semen parameters are generally not able to distinguish between fertile and infertile men, they can provide clinically useful information on time-to-pregnancy for counseling patients seeking fertility treatment. Compared to the conventional semen parameters, TPMC might be a better index for evaluating the severity of male infertility. STUDY DESIGN, SIZE, DURATION: We used data from a longitudinal cohort study on subfertile men from 2002 to 2017 and included 6061 men with initial semen analysis (SA) in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Men from subfertile couples who underwent a SA within the study period were included, and 5-year follow-up data were collected to capture conception data. Couples were further categorized into two subgroups: natural conception (n = 5126), after separating those who achieved conception using ART or IUI; natural conception without major female factor (n = 3753), after separating those with severe female factor infertility diagnoses. TPMC was calculated by multiplying the semen volume (ml) by sperm concentration (million/ml) and the percentage of progressively motile sperm (%). Cox proportional hazard models were used to report hazard ratios (HRs) with 95% CIs before and after adjusting for male age, the number of previous children before the first SA, and income. Using the regression tree method, we calculated thresholds for total sperm count, sperm concentration, progressive motility, and TPMC to best differentiate those who were more likely to conceive within 5 years after first SA from those less likely to conceive. We also plotted continuous values of semen parameters in predicting 5-year conception rates and time-to-conception. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, the median time to conception was 22 months (95% CI: 21-23). A total of 3957 (65%) couples were known to have achieved conception within 5 years of the first SA. These patients were younger and had higher values of sperm concentration, progressive motility, and TPMC. In the overall cohort, a TPMC of 50 million best differentiated men who were more likely to father a child within 5 years. Partners of men with TPMC ≥50 million had a 45% greater chance of conception within 5 years in the adjusted model (HR: 1.45; 95% CI: 1.34-1.58) and achieved pregnancy earlier compared to those men with TPMC < 50 million (median 19 months (95% CI: 18-20) versus 36 months (95% CI: 32-41)). Similar results were observed in the natural conception cohort. For the natural conception cohort without major female factor, the TPMC cut-off was 20 million. In the visual assessment of the graphs for the continuous semen parameter values, 5-year conception rates and time-to-conception consistently plateaued at higher values of sperm concentration, total sperm count, progressive motility, and TPMC compared to the WHO reference levels and our calculated thresholds. For TPMC, values up to 100-150 million were still associated with a better conception rate and time-to-conception in the visual assessment of the curves. LIMITATIONS, REASONS FOR CAUTION: There was limited information on female partners and potential for inaccuracies in capturing less severe female infertility diagnoses. Also we lacked details on assisted pregnancies achieved outside of our healthcare network (with possible miscoding as 'natural conception' in our cohort). We only used the initial SA and sperm morphology, another potentially important parameter, was not included in the analyses. We had no information on continuity of pregnancy attempts/intention, which could affect the time-to-conception data. Finally, most couples had been attempting conception for >12 months prior to initiating fertility treatment, so it is likely that we are underestimating time to conception. Importantly, our data might lack the generalizability to other populations. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that a TPMC threshold of 50 million sperm provided the best predictive power to estimate earlier time-to-conception in couples evaluated for male factor infertility. Higher values of sperm count, concentration and progressive motility beyond the WHO references were still associated with better conception rates and time-to-conception. This provides an opportunity to optimize semen parameters in those with semen values that are low but not abnormal according to the WHO reference values. These data can be used to better inform patients regarding their chances of conception per year when SA results are used for patient counseling. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Shared genetics between nonobstructive azoospermia and primary ovarian insufficiency.

Objective: Primary ovarian insufficiency (POI) and Non-obstructive azoospermia (NOA) both represent disease states of early, and often complete, failure of gametogenesis. Because oogenesis and spermatogenesis share the same conserved steps in meiosis I, it is possible that inherited defects in meiosis I could lead to shared causes of both POI and NOA. Currently, known genes that contribute to both POI and NOA are limited. In this review article, we provide a systematic review of genetic mutations in which both POI and NOA phenotypes exist. Evidence Review: A PubMed literature review was conducted from January 1, 2000 through October 2020. We included all studies that demonstrated human cases of POI or NOA due to a specific genetic mutation either within the same family or in separate families. Results: We identified 33 papers that encompassed 10 genes of interest with mutations implicated in both NOA and POI. The genes were all involved in processes of meiosis I. Conclusion: Mutations in genes involved in processes of meiosis I may cause both NOA and POI. Identifying these unique phenotypes among shared genotypes leads to biologic plausibility that the key error occurs early in gametogenesis with an etiology shared among both male and female offspring. From a clinical standpoint, this shared relationship may help us better understand and identify individuals at high risk for gonadal failure within families and suggests that clinicians obtain history for opposite sex family members when approaching a new diagnosis of POI or NOA.

What Every Gynecologist Should Know About Perimenopause.

Perimenopause often represents a physiologically challenging phase in women's lives. The clinical presentation of the perimenopause includes infertility, irregular menstrual cycles, menorrhagia, and new onset of or worsening of mood disorders. Unlike menopause, which is characterized by low levels of estradiol and progesterone, the hallmark of perimenopause is highly variable levels of estradiol and progesterone with abrupt increases and decreases that are often described as a hormonal roller coaster. This chapter invites general gynecologists to understand the hormonal basis of the common complaints of perimenopause and offers information about the physiology of these issues and helpful treatment options.

Factors associated with counseling and postoperative hormone therapy use in surgically menopausal women.

OBJECTIVE: To determine the rates of and factors associated with preoperative counseling about menopausal symptoms and use of hormone therapy postoperatively in surgically menopausal women. METHODS: This retrospective chart review included patients who underwent bilateral oophorectomies before age 52 at an academic institution during a 3-year period. We used descriptive analyses to characterize the sample and logistic regression to identify factors associated with preoperative counseling about and postoperative systemic hormone therapy for menopausal symptoms. RESULTS: This review included 152 patients with a mean age of 44 ±â€Š5 years (range 28-51). The indications for surgery were risk reduction (66%), BRCA positive (35%), and history of breast cancer (38%). One-third of women were not counseled preoperatively about menopausal symptoms. Women with cardiovascular disease and older age were less likely to receive preoperative counseling. Preoperative counseling was positively associated with risk reducing surgery.Out of 124 women with postoperative data regarding symptoms and treatment, 90 (73%) experienced vasomotor symptoms, 33 (27%) received hormone therapy (systemic or vaginal), 61 (49%) received other therapies, and 41 (33%) did not receive therapy. Younger age and negative history of breast cancer were significantly associated with systemic estrogen therapy use. CONCLUSIONS: Within our cohort, 66% had no documentation of counseling about menopausal symptoms before surgical menopause. Most women experienced symptoms postoperatively, but less than one-third of symptomatic women received hormone therapy. We have an opportunity to improve anticipatory guidance and informed consent for women undergoing surgical menopause.

Adherence to cervical cancer screening guidelines by gynecologists in the Pacific Northwest.

OBJECTIVE: In 2012, US organizations released updated cervical cancer screening guidelines calling for less frequent screening. We surveyed practicing gynecologists in the Pacific Northwest region to understand their screening practices, gauge their uptake of the new guidelines, and identify reasons why they may not follow the new guidelines. MATERIAL AND METHODS: Gynecologists from Washington, Oregon, Montana, and Idaho were sent an online survey on behalf of their state's medical association. The survey consisted of 9 questions on sex, practice setting, community size, cervical cancer screening practices, and reasons for not following the 2012 guidelines. RESULTS: Of 947 gynecologists, 123 (13.0%) completed the survey. Sixty-four respondents (52.0%) reported that they follow or plan to follow the new guidelines. Reasons cited for not following the new guidelines included concern over missed opportunities for women's health education (43 respondents or 72.9%), patients wanting more frequent screening (39 respondents or 66.1%), and concern about missing dysplasia or cancerous lesions (28 respondents or 47.5%). Although the new guidelines call for a 3-year interval between routine Pap tests or a 5-year interval between routine Pap/human papillomavirus cotests, 75 gynecologist respondents (61.0%) still recommended annual or biannual Pap screening for patients younger than 30 years, and 55 respondents (67.9%) recommended rescreening within 3 years for women 30 years and older with negative cotest results. CONCLUSIONS: While over half of the gynecologist survey respondents reported adherence or planned adherence to the 2012 guidelines, over half also reported using screening schedules that are more frequent than recommended by new guidelines. Concerns highlighted by survey participants provide an opportunity for physician and patient education on the evidence supporting the new guidelines.