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Background Cadmium is an endocrine disrupting chemical that affects the hypothalamic-pituitary-gonadal axis. Though evidence suggests its potential role in altering androgen synthesis and metabolic pathways that are characteristic of polycystic ovary syndrome (PCOS), its relation in healthy women of reproductive age is largely unknown. As women with mild sub-clinical features of PCOS who do not meet the diagnostic criteria of PCOS may still experience reduced fecundability, investigating associations between cadmium and PCOS-phenotypes among healthy women may provide unique insight into the reproductive implications for many on the PCOS spectrum. Therefore, the objective of this study was to evaluate associations between cadmium and androgens, anti-Müllerian hormone (AMH), and metabolic markers in women of reproductive age. Methods This was a prospective cohort study of 251 healthy premenopausal women without self-reported PCOS (mean age 27.3 years and BMI 24.1 kg/m2). Cadmium was measured in blood collected at baseline. Reproductive hormones and metabolic markers were measured in fasting serum 8 times per menstrual cycle for 2 cycles. Linear mixed models and Poisson regression with a robust error variance were used to examine associations between cadmium and reproductive hormones and metabolic markers and anovulation, respectively. Results Median (interquartile range) blood cadmium concentrations at baseline were 0.30 (0.19–0.43) µg/L. Higher levels of testosterone (2.2 %, 95 % confidence interval [CI] 0.4, 4.1), sex hormone-binding globulin (2.9 %, 95 % CI 0.5, 5.5), and AMH (7.7 %, 95 % CI 1.1, 14.9) were observed per 0.1 µg/L increase in cadmium concentrations. An 18 % higher probability of a mild PCOS-phenotype (95 % CI 1.06, 1.31), defined by a menstrual cycle being in the highest quartile of cycle-averaged testosterone and AMH levels, was also found per 0.1 µg/L increase in cadmium levels. No associations were observed for insulin and glucose. These findings were consistent even after analyses were restricted to non-smokers or further adjusted for dietary factors to account for potential sources of exposure. Conclusions Overall, among healthy reproductive-aged women, cadmium was associated with endocrine features central to PCOS, but not with metabolic markers. These suggest its potential role in the hormonal milieu associated with PCOS even at low levels of exposure.

In vitro fertilization is indicated for infertile women with polycystic ovarian syndrome (PCOS) after unsuccessful treatment with ovulation induction agents or in women deemed high-risk of multiple gestations who are ideal candidates for single embryo transfers. PCOS patients are at increased risk of ovarian hyperstimulation syndrome; therefore, attention should be made in the choice of in vitro fertilization treatment protocol, dose of gonadotropin utilized, and regimen to achieve final oocyte maturation. Adopting these strategies in addition to close monitoring may significantly reduce the ovarian hyperstimulation syndrome risk. Future developments may improve pregnancy outcomes and decrease complications in PCOS women undergoing fertility treatment.

Anti-müllerian hormone (AMH) is an established marker of ovarian reserve that decreases with age. Though the pool of ovarian follicles is established during fetal development, impacts of in utero exposures on AMH are uncertain. Thus, we sought to evaluate associations of in utero exposures with AMH of adult daughters with a prospective cohort study of adult daughters at university medical centers. Women noted their mother’s reported use of diethylstilbestrol (DES), vitamins, tobacco, alcohol, and caffeine during pregnancy, and their mother’s occupation during pregnancy. All participants were reproductive age women (18–40 years) enrolled in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial. Serum AMH concentrations were measured at baseline prior to conception and categorized using clinical guidelines. Multinomial regression models estimated associations between each exposure and high (>3.5 ng/mL) and low (

Objective To describe fertility characteristics, outcomes of oocyte cryopreservation cycles, and safety of ovarian stimulation in patients with GATA binding protein 2 (GATA2) deficiency, dedicator of cytokinesis 8 (DOCK8) deficiency, and sickle cell disease (SCD) preparing for hematopoetic stem cell transplantation (HSCT). Design Retrospective case series. Setting The National Institutes of Health. Patient(s) Female patients with GATA2 deficiency, DOCK8 deficiency, and SCD aged between 13 and 38 years. Intervention(s) None. Main Outcome Measure(s) Demographic and ovarian reserve parameters, stimulation outcomes, and adverse event occurrences were collected through chart review. Descriptive statistics were used to identify trends within disease subcategories. Result(s) Twenty-one women with GATA2 deficiency, DOCK8 deficiency, and SCD underwent fertility preservation prior to HSCT. Patients with DOCK8 deficiency had the lowest mean age (16.5 years old) and antimullerian hormone (0.85 ng/mL). Patients with GATA2 deficiency had the highest antral follicle count and antimullerian hormone (25.77 and 5.07 ng/mL, respectively). Baseline follicle-stimulating hormone, luteinizing hormone, and estradiol were comparable between the cohorts. The duration of stimulation was similar (10.43 to 11.25 days) across all groups. Comparable peak estradiol levels were achieved across the cohorts. Patients with SCD had the highest mature (MII) oocyte yield (10.71). Three patients experienced complications related to stimulation: pain crisis in a patient with SCD, pulmonary embolism, and zero oocytes cryopreserved in a patient with GATA2 deficiency. Conclusion(s) This study offers insight into controlled ovarian stimulation in patients with these conditions prior to HSCT. Oocyte cryopreservation can be performed successfully, although adverse events must be considered. Following the outcomes of gamete use in this cohort will serve to further our knowledge of the true reproductive potential of this population.

BACKGROUND: Attaining pregnancy is conditional upon a series of complex processes, including adequately timed intercourse, ovulation, fertilization, and implantation. Anovulation is a first line treatment target for couples with difficulty conceiving and is frequently examined in studies of fecundability. OBJECTIVES: To identify whether sporadic anovulation is an important determinant of cumulative pregnancy rates and time to pregnancy among fertile women with regular menstrual cycles. METHODS: We simulated cumulative pregnancy rates and time to pregnancy for 12 consecutive menstrual cycles among 100,000 women based on data-driven probabilities of implantation, fertilization, ovulation, and intercourse occurring in the fertile window. We assumed anovulation probabilities of 1%, 8%, or 14.5% and intercourse averaging once per week, every other day, and daily. The model incorporated reductions in implantation and fertilization rates for successive cycles of non-pregnancy. RESULTS: After 12 cycles, a reduction in the per-cycle incidence of anovulation from 14.5% to 1% resulted in a 4.0% higher cumulative pregnancy rate (86.7 versus 90.7%) and similar time to pregnancy (1-cycle median difference). In contrast, increasing mean unscheduled sexual intercourse frequency from weekly to every other day was associated with a 5-cycle median reduction in time to pregnancy (weekly: 7 cycles; every other day or daily: 2 cycles) and a 28.9% increase in the cumulative pregnancy rate (weekly: 59.9%, every other day: 88.8%; daily: 91.6%). CONCLUSIONS: In presumed fertile women with regular menstrual cycles, routine investigation of anovulation may not be an informative outcome in studies of fecundability, and routine testing to ensure ovulation and treatment of anovulation are unlikely to be medically necessary. While biomarkers or cervical fluid may help time intercourse to the fertile window, time to pregnancy can also be improved through increasing the frequency of unscheduled intercourse. These findings need corroboration in large preconception time to pregnancy studies.

Background Opioids are commonly prescribed to women of reproductive age, including after delivery and miscarriage. However, to our knowledge, opioid use has not been frequently studied in relation to the common reproductive complications of impaired fecundability and pregnancy. We examined the association of opioid use during the critical window of pregnancy establishment with fecundability and pregnancy loss. Methods We measured opioid use by urine screening and self-report at multiple time points during preconception and early pregnancy in a prospective cohort of women attempting conception (n=1228). The main outcomes included time to hCG-detected pregnancy and incidence of live birth and pregnancy loss. We estimated fecundability odds ratios (FOR) and risk ratios (RR) with 95% confidence intervals (CI) adjusting for sociodemographic characteristics, reproductive characteristics, and use of antidepressants, tobacco, alcohol, and marijuana. Results Prevalence of preconception opioid use was 18% (n=226 of 1228), and in early pregnancy was 5% (n=33 of 685). Opioid use while attempting pregnancy was associated with reduced fecundability (FOR: 0.71; 95% CI: 0.50, 1.0). Risk of pregnancy loss increased as opioid exposure was detected later in gestation, from the beginning of the cycle of conception (RR: 1.5; 95% CI 0.85, 2.6), to week 4 of pregnancy (RR: 2.1; 95% CI: 1.1, 4.1), and to week 4 and 8 of pregnancy (RR: 2.5; 95% CI: 1.3, 5.0). Conclusions Our results are consistent with the hypothesis that opioid exposure while trying to conceive may be harmful, even among healthy, non-opioid-dependent women. Possible risks to fecundability and pregnancy viability are relevant to patients and providers when evaluating pain management approaches.ClinicalTrials.gov registration number: #NCT00467363.

Background Inflammation and elevated blood lipids are associated with infertility. Aspirin and statin therapy may improve infertility treatment outcomes among overweight and obese women with systemic inflammation, but little is known about the short-term effects of statins in this population. We conducted a pilot study of aspirin, pravastatin, or combined treatment among a group of overweight and obese, reproductive-aged women. Our goal was to characterize short-term changes in inflammatory and lipid biomarkers during and after treatment. Methods In this open-label trial, women aged 18–40 years with a body mass index ≥25 kg/m2 were randomized to receive either 162 mg aspirin, 40 mg pravastatin, or both. The study medication was taken daily for 2 weeks, and participants were then followed for a two-week washout period. Participants provided blood samples at baseline, after the intervention period, and after the washout period. The outcomes were changes in biomarkers of inflammation and lipids measured in blood components at each timepoint. Results Nine, 8, and 8 women were randomized to the aspirin, pravastatin, and combined arms, respectively. Analyses were conducted among 8, 7, and 7 women in the aspirin, pravastatin, and combined arms for whom biomarker data was available at baseline. High-sensitivity C-reactive protein (hsCRP) levels were lower after treatment in all arms and continued to decrease after washout in the pravastatin and combined arms. Results were consistent between the whole sample and women with baseline hsCRP between 2 and 10 mg/L. Low-density lipoprotein (LDL) cholesterol was lower after treatment in the pravastatin and combined arms and rose slightly after washout. Conclusions Our results provide preliminary evidence that short-term aspirin and pravastatin therapy reduces hsCRP and LDL cholesterol among overweight and obese women of reproductive age, including those with low-grade inflammation. Because of these short-term effects, these drugs may improve infertility treatment outcomes in this population, which we will assess in a future randomized trial.

To examine the relationship of preconception hemoglobin A1c, a marker of cumulative exposure to glucose over the preceding 2-3 months, with time to pregnancy, pregnancy loss, and live birth among fecund women without diagnosed diabetes or other medical diseases.A secondary analysis of a prospective cohort of women participating in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial.Four US academic medical centers.A total of 1,194 healthy women aged 18-40 years with a history of one or two pregnancy losses attempting spontaneous conception were observed for up to six cycles while attempting pregnancy and throughout pregnancy if they conceived.Not applicable.Time to pregnancy, human chorionic gonadotropin pregnancy, clinical pregnancy, pregnancy loss, and live birth.Although increasing preconception A1c level was associated with reduced fecundability (fecundability odds ratio [FOR] per unit increase in A1c 0.74; 95% confidence interval [CI] 0.57, 0.96) in unadjusted models and models adjusted for age, race, smoking and treatment arm (FOR 0.79; 95% CI 0.60, 1.04), results were attenuated after further adjustment for body mass index (FOR 0.91; 95% CI 0.68, 1.21). Preconception A1c levels among women without diagnosed diabetes were not associated with live birth or pregnancy loss.Among healthy women without diagnosed diabetes, we observed no association of A1c with live birth or pregnancy loss. The association between A1c and fecundability was influenced by body mass index, a strong risk factor for both diabetes and infertility. These data support current recommendations that preconception A1c screening should be reserved for patients with risk factors for diabetes.ClinicalTrials.gov: NCT00467363.

The novel coronavirus disease 2019 (COVID-19) has rapidly spread around the world, impacting every aspect of life. Valuable research is currently being conducted to understand disease transmission, detection, and treatment. As countries begin to relax policies aimed to reduce disease transmission, contact tracing and antibody testing will likely be incorporated to slow the spread of COVID-19. However, future research is needed to determine if the presence of COVID-19 antibodies offers immunity.

OBJECTIVE To characterize variation in circulating vascular endothelial growth factor (VEGF) and its receptor, soluble fms-like tyrosine kinase-1 (sFLT-1), across the menstrual cycle in normal ovulating women in relation to reproductive hormones to identify the utility of VEGF and sFLT-1 as peripheral biomarkers of endometrial remodeling. METHODS Ninety-six healthy, regularly menstruating ovulatory women, aged 18-44 years, enrolled in the BioCycle Study, a prospective cohort study at a U.S. academic research center. Vascular endothelial growth factor and sFLT-1 were measured in concurrently collected plasma, serum, and urine up to eight times across a single cycle. Reproductive hormones were measured in serum. Mean concentrations of VEGF and sFLT-1 were compared across phases of the cycle, and correlations between specimen types were calculated. Harmonic models estimated associations between VEGF and sFLT-1 and characteristics of hormonal patterns. RESULTS No variation in VEGF or sFLT-1 levels were detected over the menstrual cycle. Median (25th percentile, 75th percentile) concentrations of VEGF during the menstrual cycle were 31.2 pg/mL (24.1, 56.9) in plasma, 194.1 pg/mL (125.4, 350.2) in serum, and 101.7 pg/mL (64.2, 165.8) in urine. Plasma and serum measures were consistently correlated, whereas urinary measures were not. Vascular endothelial growth factor was not consistently associated with reproductive hormone concentrations, although sFLT-1 was associated with higher mean and amplitude of estradiol. CONCLUSION Circulating VEGF and sFLT-1 did not vary across the menstrual cycle and therefore are unlikely to be useful peripheral biomarkers of endometrial changes across the menstrual cycle. For studies measuring circulating VEGF for other reasons, plasma may be the preferred medium and timing to menstrual cycle phase need not be considered for reproductive-age women.

Concerns remain about the health of children conceived by infertility treatment. Studies to date have predominantly not identified substantial long-term health effects after accounting for plurality, which is reassuring given the increasing numbers of children conceived by infertility treatment worldwide. However, as technological advances in treatment arise, ongoing studies remain critical for monitoring health effects. To study whether the techniques used in infertility treatment cause health differences, however, remains challenging due to identification of an appropriate comparison group, heterogeneous treatment, and confounding by the underlying causes of infertility. In fact, the factors that are associated with underlying infertility, including parental obesity and other specific male and female factors, may be important independent factors to consider. This review will summarize key methodological considerations in studying children conceived by infertility treatment including the evidence of associations between underlying infertility factors and child health.

PURPOSE: To describe controlled ovarian stimulation (COS) in a population of women with GATA2 deficiency, a genetic bone marrow failure syndrome, prior to allogeneic hematopoietic stem cell transplant METHODS: This is a retrospective case series of nine women with GATA2 deficiency who underwent oocyte preservation at a research institution. Main outcomes measured include baseline fertility characteristics ((antimullerian hormone (AMH) and day 3 follicle-stimulating hormone (FSH) and estradiol (E2)) and total doses of FSH and human menopausal gonadotropins (HMG), E2 on day of trigger, and total number of metaphase II oocytes retrieved. RESULTS: The mean age was 24 years [16–32], mean AMH was 5.2 ng/mL [0.7–10], and day 3 mean FSH was 5.1 U/L [0.7–8.1], and E2 was 31.5 pg/mL [

Background Isolated absent thelarche is a rare condition that is infrequently reviewed in the literature. Case A 28-year-old woman with neurofibromatosis type 1 and acromegaly presented with absent breast development despite hormone therapy. Examination noted a normally developed woman with acromegalic features and Tanner stage I breasts. Hormone studies and karyotype were normal. Magnetic resonance imaging of the patient's brain demonstrated a voluminous pituitary. Chromosome microarray analysis diagnosed the neurofibromatosis 1 microdeletion syndrome. Breast ultrasonography and surgical consultation were offered. Conclusions Neither neurofibromatosis type 1, acromegaly, nor neurofibromatosis 1 microdeletion syndrome are linked to absent thelarche. After attempting hormone therapy, patients with absent thelarche should be evaluated for congenital breast anomalies, estrogen receptor abnormalities, or gene defects. Psychological and surgical consultation should also be offered.

STUDY QUESTIONIs cannabis use assessed via urinary metabolites and self-report during preconception associated with fecundability, live birth and pregnancy loss?SUMMARY ANSWERPreconception cannabis use was associated with reduced fecundability among women with a history of pregnancy loss attempting pregnancy despite an increased frequency of intercourse.WHAT IS KNOWN ALREADYCannabis use continues to rise despite limited evidence of safety during critical windows of pregnancy establishment. While existing studies suggest that self-reported cannabis use is not associated with fecundability, self-report may not be reliable.STUDY DESIGN, SIZE, DURATIONA prospective cohort study was carried out including 1228 women followed for up to six cycles while attempting pregnancy (2006 to 2012), and throughout pregnancy if they conceived.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen aged 18–40 years with a history of pregnancy loss (n = 1228) were recruited from four clinical centers. Women self-reported preconception cannabis use at baseline and urinary tetrahydrocannabinol metabolites were measured throughout preconception and early pregnancy (up to four times during the study: at baseline, after 6 months of follow-up or at the beginning of the conception cycle, and weeks 4 and 8 of pregnancy). Time to hCG-detected pregnancy, and incidence of live birth and pregnancy loss were prospectively assessed. Fecundability odds ratios (FOR) and 95% CI were estimated using discrete time Cox proportional hazards models, and risk ratios (RRs) and 95% CI using log-binomial regression adjusting for age, race, BMI, education level, baseline urine cotinine, alcohol use and antidepressant use.MAIN RESULTS AND THE ROLE OF CHANCEPreconception cannabis use was 5% (62/1228), based on combined urinary metabolite measurements and self-report, and 1.3% (11/789) used cannabis during the first 8 weeks of gestation based on urinary metabolites only. Women with preconception cannabis use had reduced fecundability (FOR 0.59; 95% CI 0.38, 0.92). Preconception cannabis use was also associated with increased frequency of intercourse per cycle (9.4 ± 7 versus 7.5 ± 7 days; P = 0.02) and higher LH (percentage change 64%, 95% CI 3, 161) and higher LH:FSH ratio (percentage change 39%, 95% CI 7, 81). There were also suggestive, though imprecise, associations with anovulation (RR 1.92, 95% CI 0.88, 4.18), and live birth (42% (19/45) cannabis users versus 55% (578/1043) nonusers; RR 0.80, 95% CI 0.57, 1.12). No associations were observed between preconception cannabis use and pregnancy loss (RR 0.81, 95% CI 0.46, 1.42). Similar results were observed after additional adjustment for parity, income, employment status and stress. We were unable to estimate associations between cannabis use during early pregnancy and pregnancy loss due to limited sample size.LIMITATIONS, REASONS FOR CAUTIONOwing to the relatively few cannabis users in our study, we had limited ability to make conclusions regarding live birth and pregnancy loss, and were unable to account for male partner use. While results were similar after excluding smokers, alcohol use and any drug use in the past year, some residual confounding may persist due to these potential co-exposures.WIDER IMPLICATIONS OF THE FINDINGSThese findings highlight potential risks on fecundability among women attempting pregnancy with a history of pregnancy loss and the need for expanded evidence regarding the reproductive health effects of cannabis use in the current climate of increasing legalization.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract numbers: HHSN267200603423, HHSN267200603424, HHSN267200603426, HHSN275201300023I). Jeannie G. Radoc has been funded by the National Institutes of Health Medical Research Scholars Program, a public–private partnership supported jointly by the National Institutes of Health and generous contributions to the Foundation for the National Institutes of Health from the Doris Duke Charitable Foundation (DDCF Grant # 2014194), Genentech, Elsevier, and other private donors. The authors report no conflict of interest in this work and have nothing to disclose.TRIAL REGISTRATION NUMBERClinicaltrials.gov NCT00467363

“Mystery, Medicine, and the Magnificent Mile,” the theme for the annual Midwest Reproductive Symposium International (MRSi) in Chicago, IL, captured the attention of reproductive professionals all over the world. Each year, the conference agenda encompasses emerging technologies in assisted reproduction, updates in the management of reproductive diseases, and common challenges encountered in clinical practice. The structure of the meeting, offering a mixture of lectures, panel discussions, and interactive workshops, creates a collaborative environment for physicians, geneticists, embryologists, nurses, mental health professionals, basic scientists, business administrative professionals, reproductive endocrinology and infertility fellows, and obstetrics and gynecology residents. The goal of the MRSi meeting is to provide all reproductive professionals the opportunity to exchange ideas, foster relationships, and deliver quality patient care. As the field continues to evolve, MRSi provides an exciting venue to uncover the mysteries of reproductive medicine with enthusiasm and collaboration.

OBJECTIVES: Marijuana is the most widely used and fastest growing drug in the United States, with legislation currently broadening legalization for both medical and recreational use. However, there are limited data evaluating associations with fecundity and adverse pregnancy outcomes. A few studies evaluating self-reported use suggest marijuana may not be harmful for pregnancy, yet there is a concern for underreporting due to stigma as marijuana is not universally legalized. Our aim was to examine the association between preconception marijuana use, using both self-reported and urinary levels of tetrahydrocannabinol (THC), and fecundability, live birth, and pregnancy loss. METHODS: Women aged 18–40 years old (n = 1212) enrolled in the EAGeR trial were screened for urinary THC at up to 2 time points during preconception using a homogenous enzyme immunoassay from Randox Laboratories, and asked at baseline to report any marijuana use during the past year. Women were followed for up to 6 months while attempting pregnancy. Cox proportional hazard regression was used to calculate fecundability odds ratios (FOR), and log-binomial regression to estimate risk ratios (RR) for live birth and pregnancy loss adjusting for age, race, BMI, education, smoking, alcohol, and detectable levels of opioids. RESULTS: 33 (2.7%) women screened positive for THC during the preconception period, of which 14 also self-reported use during the past year. 62 women (5.1%) either screened positive or self-reported use. Women who screened positive for preconception THC had reduced fecundability (FOR 0.50; 95% CI 0.25, 1.00), as well as women who self-reported marijuana use (FOR 0.54; 95% CI 0.31, 0.94), or who were positive using either urinary or self-report (FOR 0.53, 95% CI 0.33, 0.86). No associations were observed between marijuana use and live birth (RR 0.71; 95% CI 0.41, 1.22) and pregnancy loss (RR 0.78; 95% CI 0.28, 2.18). CONCLUSIONS: Women who screened positive for THC during preconception, or self-reported use during the past year had reduced fecundability, though no associations were observed with live birth or pregnancy loss. Further investigations are needed to determine what duration and dose of marijuana may negatively impact fecundability. FUNDING SOURCES: Intramural Research Program, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development.

BACKGROUND: Although nausea and vaginal bleeding are commonly experienced in early pregnancy, their prognostic value in predicting clinical pregnancy loss is not well understood. OBJECTIVE: This study aimed to understand whether timing of bleeding and nausea symptoms can be used to predict risk of pregnancy loss among women with ultrasound-confirmed pregnancies. STUDY DESIGN: A cohort of 701 women with clinically confirmed pregnancies and 1 to 2 previous pregnancy losses were preconceptionally enrolled in the Effects of Aspirin in Gestation and Reproduction trial (2006–2012). Participants completed daily symptom diaries from 2 to 8 weeks’ gestation and were prospectively monitored for detection of pregnancy loss. The risk of pregnancy loss was estimated for each observed bleeding and nausea pattern, and positive and negative predictive values for each pattern were calculated. RESULTS: Among 701 women, 211 (30.1%) reported any vaginal bleeding, and 639 (91.2%) reported any nausea. Most bleeding experienced by women was spotting and contained within a single episode. Within 2 to

Objective To compare live birth and multiple gestation in patients diagnosed with unexplained infertility undergoing intrauterine insemination after ovarian stimulation (OS-IUI) with oral medications versus gonadotropins. Design Systemic review and meta-analysis. Setting Not applicable. Patient(s) Patients undergoing OS-IUI for treatment of unexplained infertility. Intervention(s) Clomiphene, letrozole, or gonadotropins for OS-IUI. Main Outcome Measure(s) Live birth and multiple gestation. Result(s) Eight total trials were identified that met the inclusion criteria and comprised 2,989 patients undergoing 6,590 cycles. One study reported a significant increase in both live births and multiple gestations with the use of gonadotropins, two studies found an increased likelihood of live birth with the use of gonadotropins, and two studies found an increased risk of twins with gonadotropins. The relative risk of live birth in subjects receiving gonadotropins was 1.09. The relative risk of multiple gestation in subjects receiving gonadotropins was 1.06. Clinical pregnancy was higher in protocols with lax cancellation policies or higher gonadotropin doses, with subsequent increased relative risks of multiple gestations of 1.20 and 1.15, respectively. Singleton births per subject were similar between the two groups. The results did not change in per-protocol, per cycle, or fixed-effect model sensitivity analyses. Conclusion(s) For every birth gained with the use of gonadotropins, a similar increased risk of multiple gestation occurs. The randomized data do not support the use of gonadotropin for OS-IUI in women with unexplained infertility. Clinical Trial Registration Number Prospero CRD4201911998

This study is aimed at comparing clinical pregnancy rates (CPRs) in patients who are administered either gonadotropin-releasing hormone agonist (GnRHa) or human chorionic gonadotropin (hCG) for ovulation trigger in intrauterine insemination (IUI) cycles. A prospective randomized comparative study was conducted at Hue University Hospital in Vietnam. A total of 197 infertile women were randomly assigned to receive either GnRHa trigger (n=98 cycles) or hCG trigger (n=99 cycles) for ovulation trigger. Patients returned for ultrasound monitoring 24 hours after IUI to confirm ovulation. A clinical pregnancy was defined as the presence of gestational sac with fetal cardiac activity. There was no difference in ovulation rates in either group receiving GnRHa or hCG trigger for ovulation. Biochemical and CPR were higher in patients who received hCG (28.3% and 23.2%) versus GnRHa (14.3% and 13.3%) (p=0.023, OR 0.42, 95%CI=0.21−0.86 and p=0.096, OR 0.51, 95%CI=0.24−1.07, respectively). After adjusting for body mass index (BMI) and infertility duration, there was no difference in CPR between the two groups (OR 0.58, 95% CI 0.27-1.25, p=0.163). In conclusion, the use of the GnRHa to trigger ovulation in patients undergoing ovulation induction may be considered in patients treated with IUI.

Assisted reproductive technology (ART) encompasses all procedures that manipulate the oocytes, sperm, and embryos outside of the body. Decades of research have allowed the field to emerge as a reliable and safe treatment for infertile men and women. Indications for in vitro fertilization (IVF) include tubal factor infertility, anovulation, male factor infertility, and decreased ovarian reserve. Treatment is not limited to the infertile population, as IVF with preimplantation genetic diagnosis also offers patients an opportunity to prevent transmission of a genetic condition for which they have been found to carry. The field of ART continues to rapidly evolve, as more knowledge is gained from studies reporting on ovarian stimulation protocols, reproductive techniques such as intracytoplasmic sperm injection, and blastocyst transfer. Techniques are aimed to improve live birth rates while ensuring the optimal health of children conceived using IVF. This review contains 8 figures, 5 tables and 63 references Key Words: assisted reproductive technology, blastocyst, decreased ovarian reserve, embryo transfer, gonadotropin-releasing hormone agonist, gonadotropin-releasing hormone antagonist, intracytoplasmic sperm injection, luteal phase support, ovarian hyperstimulation syndrome, vitrification

For the majority of infertility patients, ovulation induction is the initial therapy. Treatment is individualized for a couple based on ovarian reserve testing, semen analysis, and the presence of anatomic pathology. Candidates for ovulation induction include those who are anovulatory and couples with unexplained infertility. The majority of patients diagnosed with anovulation have polycystic ovarian syndrome. Treatment options include clomiphene citrate and letrozole. For patients with hypogonadotropic hypogonadism, treatment involves injections with gonadotropins. Treatment is typically combined with intrauterine insemination to maximize pregnancy rates, especially in patients with male factor infertility or unexplained infertility. A stepwise approach is necessary, as patients who are unsuccessful with less invasive and costly treatments may eventually require in vitro fertilization. This review contains 7 figures, 3 tables and 57 references Key Words: clomiphene citrate, gonadotropins, infertility, intrauterine insemination, letrozole, ovulation induction, polycystic ovarian syndrome, unexplained infertility

In 2009, the World Health Organization formally recognized infertility as a disease of the reproductive system. This designation serves to ease access to infertility evaluation and treatment. Infertility is a disease of both men and women, and proper evaluation of both partners is necessary. Common causes of infertility are ovulatory dysfunction, tubal and pelvic pathology, unexplained infertility, and male factor. A complete history and physical examination may uncover the underlying etiology, although verification of tubal patency and normal semen analysis is warranted. This period also offers an opportunity to perform preconception testing and optimize women’s health before conception. Treatment for infertility is aimed to restore normal reproductive function and anatomy. In addition, patient education and counseling is indeed a very important aspect of infertility care. This review contains 5 figures, 5 tables and 60 references Key Words: anovulation, Antimullerian hormone, antral follicle count, hysterosalpingogram, infertility, infertility evaluation, ovarian reserve testing, polycystic ovarian syndrome, saline infusion sonohysterography

In 2005, the National Institutes of Health (NIH) chronic graft-versus-host disease (cGVHD) consensus project provided diagnosis and staging criteria, based mostly on clinical experience and expert opinion. These criteria were revised in 2014, aiming to provide enhanced specificity and clarity. However, the impact of 2014 changes to the original NIH cGVHD severity scoring criteria has not been reported. In this study, 284 patients, prospectively enrolled on the National Cancer Institute's cross-sectional cGVHD natural history study, were scored using the 2005 NIH cGVHD criteria and then rescored according to the 2014 modifications. In comparing the two criteria, 2014 cGVHD global severity scoring resulted in a tendency toward being categorized as milder scores (75 vs. 72% of severe score per 2014, p = 0.0009), with a statistically significant shift in NIH liver and lung scores toward milder categories (p

Usporedba NIH kriterija za kronični GVHD 2005 i 2014 godina.

The presentation of an adnexal mass in an adolescent is a concerning event for the patient and the family. Patients are most likely to present with abdominal pain or a palpable mass. The diagnostic imaging of choice is pelvic ultrasonography. The majority of these lesions are benign ovarian cysts. These cysts should be followed with ultrasound, as many will spontaneously regress. Further evaluation with laboratory tests may also be warranted, which will aid in diagnosis and treatment. Ovarian cysts that are failed to resolve, severely symptomatic, or concerned with malignancy require surgical intervention. Laparoscopy has shown to be beneficial in the adolescent population and should be the procedure of choice. In addition, ovarian conservation is the ideal treatment in order to continue normal pubertal development and preserve reproductive health.

To evaluate the effect of progesterone (P) for luteal phase support after ovulation induction (OI) and intrauterine insemination (IUI).An updated systematic review and meta-analysis.Not applicable.Patients undergoing OI-IUI for infertility.Exogenous P luteal support after OI-IUI.Live birth.Eleven trials were identified that met inclusion criteria and constituted 2,842 patients undergoing 4,065 cycles, more than doubling the sample size from the previous meta-analysis. In patients receiving gonadotropins for OI, clinical pregnancy (relative risk [RR] 1.56, 95% confidence interval [CI] 1.21-2.02) and live birth (RR 1.77, 95% CI 1.30-2.42) were more likely in P supplemented patients. These findings persisted in analysis of live birth per IUI cycle (RR 1.59, 95% CI 1.24-2.04). There were no data on live birth in clomiphene citrate or clomiphene plus gonadotropin cycles. There was no benefit on clinical pregnancy with P support for patients who underwent OI with clomiphene (RR 0.85, 95% CI 0.52-1.41) or clomiphene plus gonadotropins (RR 1.26, 95% CI 0.90-1.76).Progesterone luteal phase support is beneficial to patients undergoing ovulation induction with gonadotropins in IUI cycles. The number needed to treat is 11 patients to have one additional live birth. Progesterone support did not benefit patients undergoing ovulation induction with clomiphene citrate or clomiphene plus gonadotropins.