Establishing a Gold Standard for Quantitative Menstrual Cycle Monitoring.

Background and Objectives: The Quantum Menstrual Health Monitoring Study will measure four key reproductive hormones in the urine (follicle-stimulating hormone, FSH; estrone-3-glucuronide, E13G; luteinizing hormone, LH; and pregnanediol glucuronide, PDG) to characterize patterns that predict and confirm ovulation, referenced to serum hormones and the gold standard of the ultrasound day of ovulation in participants with regular cycles. These normal cycles will provide a reference for comparison to irregular cycles in subjects with polycystic ovarian syndrome (PCOS) and athletes. Materials and Methods: Participants will track their menstrual cycles for 3 months and be provided with an at-home urine hormone monitor (Mira monitor) to predict ovulation. The day of ovulation will be confirmed with serial ultrasounds completed in a community clinic. Urine results will be compared to serum hormone values. Other markers of menstrual health, such as bleeding patterns and temperature changes, will be determined using a customized app. Three groups will be recruited. Group 1 will include those with consistent regular cycle lengths (between 24-38 days), and will be compared to two groups with irregular cycle lengths (with increased cycle length variability and longer cycles). Group 2 will include those with polycystic ovarian syndrome (PCOS) with irregular cycles and Group 3 will include individuals participating in high levels of exercise with irregular cycles. Hypothesis: The Mira monitor quantitative urine hormone pattern will accurately correlate with serum hormonal levels and will predict (with LH) and confirm (with PDG) the ultrasound day of ovulation in those with regular cycles as well as those with irregular cycles. Rationale: Once the ultrasound validation is complete, tools like the Mira monitor with a customized app may become a new standard for at-home and remote clinical monitoring of the menstrual cycle without having to use labor-intensive follicular-tracking ultrasound or follow serum hormone changes. Conclusions: Precision monitoring of the menstrual cycle is expected to impact individuals who want to increase their menstrual health literacy and guide decisions about fertility.

The effect of testosterone on ovulatory function in transmasculine individuals.

BACKGROUND: An estimated 1.4 million persons in the United States identify as transgender or nonbinary, signifying that their gender identity does not correspond with their assigned sex at birth. Individuals assigned female at birth may seek gender-affirming hormone therapy with testosterone. No studies have directly examined ovulatory function in transmasculine individuals using injectable testosterone. OBJECTIVES: Our primary objective was to determine the effect of testosterone on ovulatory suppression in transmasculine individuals. Secondary objectives were to determine predictors of ovulation in transmasculine individuals on testosterone, and to assess the effect of testosterone on antimüllerian hormone. MATERIALS AND METHODS: This prospective observational study recruited participants from a community clinic that provides gender-affirming hormone therapy. Enrolled individuals were assigned female at birth and were currently using or seeking to initiate masculinizing therapy with injectable testosterone esters (transmasculine individuals). Over a 12-week study period, participants collected daily urine samples for pregnanediol-3-glucoronide testing and completed daily electronic bleeding diaries. We assessed monthly serum mid-dosing interval testosterone, estradiol and sex hormone binding globulin, and antimüllerian hormone values at baseline and study end. Ovulation was defined as pregnanediol-3-glucoronide greater than 5 µg/mL for 3 consecutive days. The primary outcome was the proportion of participants who ovulated during the study period. We examined predictors of ovulation such as age, length of time on testosterone, serum testosterone levels, body mass index, and bleeding pattern. RESULTS: From July to November 2018, we enrolled 32 individuals; 20 completed the study (14 continuing testosterone users, 6 new users). Median age was 23 years (range 18-37 years). Bleeding or spotting during the study period was noted by 41% of participants (13/32). Among continuing users, median testosterone therapy duration was 11 months (range 1-60 months). A single ovulation was observed out of a total of 61 combined months of testosterone use; however, several transient rises in pregnanediol-3-glucoronide followed by bleeding episodes were suggestive of 7 dysfunctional ovulatory cycles among 7 individuals. There was no difference in antimüllerian hormone from baseline to 12 weeks between participants initiating testosterone and continuing users of testosterone. We did not have the power to examine our intended predictors given the low numbers of ovulatory events, but found that longer time on testosterone and presence of vaginal bleeding over 12 weeks were associated with transient rises in pregnanediol-3-glucoronide. CONCLUSION: This study suggests that testosterone rapidly induces hypothalamic-pituitary-gonadal suppression, resulting in anovulation in a proportion of new users. Importantly, these data also suggest that some long-term testosterone users break through the hormonal suppression and experience an ovulatory event, thereby raising concerns pertaining to the need for contraception in transmasculine individuals engaged in sexual intercourse with sperm-producing partners. Given the small number of overall participants, this work is hypothesis generating. Larger studies are needed to confirm and to clarify these findings.

Pilot observational prospective cohort study on the use of a novel home-based urinary pregnanediol 3-glucuronide (PDG) test to confirm ovulation when used as adjunct to fertility awareness methods (FAMs) stage 1.

RATIONALE: Ovulation confirmation is a fundamental component of the evaluation of infertility. PURPOSE: To inform the design of a larger clinical trial to determine the effectiveness of a new home-based pregnanediol glucuronide (PDG) urine test to confirm ovulation when compared with the standard of serum progesterone. METHODS: In this observational prospective cohort study (single group assignment) in an urban setting (stage 1), a convenience sample of 25 women (aged 18-42 years) collected daily first morning urine for luteinisinghormone (LH), PDG and kept a daily record of their cervical mucus for one menstrual cycle. Serum progesterone levels were measured to confirm ovulation. Sensitivity and specificity were used as the main outcome measures. Estimation of number of ultrasound (US)-monitored cycles needed for a future study was done using an exact binomial CI approach. RESULTS: Recruitment over 3 months was achieved (n=28) primarily via natural fertility regulation social groups. With an attrition rate of 22%, specificity of the test was 100% for confirming ovulation. Sensitivity varied depending on whether a peak-fertility mucus day or a positive LH test was observed during the cycle (85%-88%). Fifty per cent of participants found the test results easy to determine. A total of 73 US-monitored cycles would be needed to offer a narrow CI between 95% and 100%. CONCLUSION: This is first study to clinically evaluate this test when used as adjunct to the fertility awareness methods. While this pilot study was not powered to validate or test efficacy, it helped to provide information on power, recruitment and retention, acceptability of the procedures and ease of its use by the participants. Given this test had a preliminary result of 100% specificity, further research with a larger clinical trial (stage 2) is recommended to both improve this technology and incorporate additional approaches to confirm ovulation. TRIAL REGISTRATION NUMBER: NCT03230084.

Home ovulation test use and stress during subfertility evaluation: Subarm of a randomized controlled trial.

OBJECTIVES: A prospective, randomized controlled trial in women seeking to conceive examined the impact of using ovulation tests on self-reported levels of stress, psychological well-being, and quality of life in women with unexplained infertility. METHOD: The test group used a home ovulation test to detect the day of ovulation, whereas the control group were provided with a predicted day of ovulation based on the average length of menstrual cycle reported during study recruitment. Volunteers collected their first morning urine samples to evaluate biochemical levels of stress (urinary cortisol and estrone-3-glucouronide) and completed questionnaires over two complete menstrual cycles. RESULTS: Overall, the use of digital ovulation tests by sub-fertile women under medical care had negligible negative effects and no detectable positive benefit on psychological well-being, according to multiple measurements of stress by questionnaire and biochemical markers. No significant differences were found between groups for all stress measures at the various study time points, except in relation to "couple concordance" where the test group scored much higher than the control group (mean difference at end of study was 21.25 (95% confidence interval: 9.25, 33.25; P = 0.0015)). The maximum difference in log cortisol: creatinine ratio between the test and control groups was -0.28 (95% confidence interval: -0.69, 0.13). CONCLUSIONS: These results do not support propositions that using digital ovulation tests can cause stress in women trying to conceive.

The majority of irregular menstrual cycles in adolescence are ovulatory: results of a prospective study.

PURPOSE: While ovulation is most likely to occur in adolescent girls with regular menstrual cycles, there are limited data on the incidence of ovulation in girls with irregular menstrual cycles in early postmenarcheal years. The aim of the study was to evaluate the presence of ovulation in healthy postmenarcheal girls with irregular menstrual cycles. METHODS, DESIGN AND SUBJECTS: Prospective cohort study over 12 weeks including 40 healthy postmenarcheal girls recruited from the population-based cohort of adolescents from Western Australian Pregnancy Cohort (Raine) Study with irregular menstrual cycles defined by either menstrual cycles <21 days or >35 days in duration or cycle length that varied from month to month by >4 days according to menstrual diaries. MAIN OUTCOME MEASURE: Ovulation defined by urinary pregnanediol-3α-glucuronide/creatinine measurements higher than three times above minimum value obtained from 12 samples (1 per week). RESULTS: Forty girls (37 Caucasians) with irregular menstrual cycles aged 15.1 (median (IQR) 14.9-15.4) years who were 2.3 (1.9-3.3) years postmenarche were assessed. Urinary pregnanediol-3α-glucuronide/creatinine values identified that 33 girls (82.5%) ovulated during the 3 months of observation and 7 girls had anovulatory cycles. Menstrual diaries collected for a median (IQR) of 159 (137.5-188.2) days showed median minimal and maximum menstrual cycle duration of 24 (11.5-29) and 38.5 (35-48) days, respectively. CONCLUSIONS: A large proportion of healthy adolescent girls with irregular menstrual cycles are still ovulating despite irregular and infrequent menses.

Ovulatory status and menstrual cycle duration assessed by self-collection of urine on pH strips in a population-based sample of French women not using hormonal contraception.

BACKGROUND: Assessing menstrual cycle function in the general population using a non-invasive method is challenging, both in non-industrialized and industrialized countries. SUBJECTS AND METHODS: The Observatory of Fecundity in France (Obseff) recruited on a nationwide basis a random sample of 943 women aged 18-44 years with unprotected intercourse. A sub-study was set up to assess the characteristics of a menstrual cycle by using a non-invasive method adapted to the general population. Voluntary women were sent a collection kit by the post and requested to collect urine samples on pH strips, together with daily recording of reproductive-related information during a full menstrual cycle. A total of 48 women collected urine every day, whereas 160 women collected urine every other day. Immunoassays were used to measure pregnanediol-3-α-glucuronide, estrone-3-glucuronide and creatinine. Ovulation occurrence and follicular phase duration were estimated using ovulation detection algorithms, compared to a gold standard consisting of three external experts in reproductive medicine. RESULTS: Every other day urine collection gave consistent results in terms of ovulation detection with every day collection (intraclass coefficient of correlation, 0.84, 95% confidence interval, 0.76-0.98). The proportion of anovulatory menstrual cycles was 8%. The characteristics of the ovulatory cycles were length 28 (26-34), follicular phase 16 (12-23), luteal phase 13 (10-16) days median (10th-90th percentiles). DISCUSSION-CONCLUSION: Assessing menstrual cycle characteristics based on urine sample spot only collected every other day in population-based studies through a non-invasive, well accepted and cost-limited procedure not requiring any direct contact with the survey team appears feasible and accurate.

Three-step method for menstrual and oral contraceptive cycle verification.

OBJECTIVES: Fluctuating endogenous and exogenous ovarian hormones may influence exercise parameters; yet control and verification of ovarian hormone status is rarely reported and limits current exercise science and sports medicine research. The purpose of this study was to determine the effectiveness of an individualised three-step method in identifying the mid-luteal or high hormone phase in endogenous and exogenous hormone cycles in recreationally-active women and determine hormone and demographic characteristics associated with unsuccessful classification. DESIGN: Cross-sectional study design. METHODS: Fifty-four recreationally-active women who were either long-term oral contraceptive users (n=28) or experiencing regular natural menstrual cycles (n=26) completed step-wise menstrual mapping, urinary ovulation prediction testing and venous blood sampling for serum/plasma hormone analysis on two days, 6-12days after positive ovulation prediction to verify ovarian hormone concentrations. RESULTS: Mid-luteal phase was successfully verified in 100% of oral contraceptive users, and 70% of naturally-menstruating women. Thirty percent of participants were classified as luteal phase deficient; when excluded, the success of the method was 89%. Lower age, body fat and longer menstrual cycles were significantly associated with luteal phase deficiency. CONCLUSIONS: A step-wise method including menstrual cycle mapping, urinary ovulation prediction and serum/plasma hormone measurement was effective at verifying ovarian hormone status. Additional consideration of age, body fat and cycle length enhanced identification of luteal phase deficiency in physically-active women. These findings enable the development of stricter exclusion criteria for female participants in research studies and minimise the influence of ovarian hormone variations within sports and exercise science and medicine research.

Tamoxifen for the treatment of breakthrough bleeding with the etonogestrel implant: a randomized controlled trial.

OBJECTIVE: The etonogestrel (ENG) subdermal implant can cause frequent breakthrough bleeding in some users. The objective of this study was to evaluate whether a short course of tamoxifen reduces bleeding/spotting days compared to placebo in ENG implant users. STUDY DESIGN: In this double-blind trial, we randomized ENG implant users with frequent or prolonged bleeding or spotting to tamoxifen 10 mg or placebo twice daily for 7 days, to be started after 3 consecutive days of bleeding/spotting. Treatment was repeated as needed up to three times in 180 days. Subjects completed a daily text message bleeding diary. A sample size of 56 provided 80% power to detect a difference of 6 days of bleeding/spotting per 30 days by two-sample t test. Ovulation was monitored by urinary metabolites of progesterone. RESULTS: From March 2014 to February 2015, 56 women enrolled. Fifty-one completed at least 30 days of follow up, and 34 completed 180 days. Compared to women randomized to placebo, women randomized to tamoxifen reported 5 fewer days of bleeding/spotting over 30 days (95% confidence interval [CI] -9.9 to -0.05, p=.05), and 15.2 more continuous bleeding-free days (95% CI 2.8-27.5 days, p=.02) after first use of study drug. Conclusions could not be drawn after 30 days due to higher-than-expected dropout. No ovulation was detected. CONCLUSION: First use of tamoxifen by ENG implant users reduces bleeding/spotting days and provides a longer cessation of bleeding/spotting than placebo, without compromising ovulation suppression. Further study is needed to determine whether this effect is maintained with repeat use. IMPLICATIONS: Women with frequent ENG implant-related breakthrough bleeding may experience a reduction in bleeding/spotting days and an increase in continuous bleeding-free days in the month following first use of tamoxifen. This short course of tamoxifen was well tolerated with bleeding cessation noted within a median of 5 days.

Antimüllerian hormone levels and numbers and sizes of antral follicles in regularly menstruating women of reproductive age referenced to true ovulation day.

OBJECTIVE: To assess menstrual cycle antimüllerian hormone (AMH) levels in reproductive age women and which/how many follicles substantially produce AMH. DESIGN: Prospective study of menstruating women using mixed-effects models to analyze AMH variability and correlation of follicle counts/size classes to AMH levels. SETTING: Clinic. PATIENT(S): Regular menstruating women with ovulatory cycles (n = 40, aged 18-37 years) and no known subfertility. INTERVENTION(S): Women collected daily urine samples and visited the study center for blood samples/transvaginal ultrasound during one complete menstrual cycle (visits were every 2 days; daily from follicle size >16 mm until postovulation). MAIN OUTCOME MEASURE(S): AMH levels throughout the menstrual cycle, correlated with antral follicles as observed by ultrasound and identification of follicles producing AMH. RESULTS: Of all antral follicles visible by high-resolution ultrasound, AMH is produced substantially only by follicles up to 7 mm in diameter. For women with basal AMH >1 ng/mL, mean AMH concentrations vary across ovulatory menstrual cycles, showing a statistically significant decrease from -5 to 2 days after objective ovulation; significantly lower mean luteal AMH levels (-7.59% to mean follicular AMH) are detected. The number of antral follicles can be estimated from AMH (ng/mL) levels using the modified Beckman Coulter Generation II AMH assay for any day of the follicular phase. CONCLUSION(S): AMH concentrations vary across ovulatory menstrual cycles, showing a significant periovulatory decrease. The number of small antral follicles can be estimated from preovulatory AMH levels with relevance for patient management. CLINICAL TRIAL REGISTRATION NUMBER: NCT01802060.

Monitoring the menstrual cycle: Comparison of urinary and serum reproductive hormones referenced to true ovulation.

OBJECTIVE: The aim of the study was to examine relationships and interindividual variations in urinary and serum reproductive hormone levels relative to ultrasound-observed ovulation in menstrual cycles of apparently normally menstruating women. METHODS: This was a prospective study of normally menstruating women (no known subfertility), aged 18-40 years (n = 40), who collected daily urine samples and attended the study centre for blood samples and transvaginal ultrasound during one complete menstrual cycle. Serum luteinising hormone (LH), progesterone, estradiol, urinary LH, pregnanediol-3- glucuronide (P3G) and estrone-3-glucuronide were measured. Ultrasound was conducted by two physicians and interpreted by central expert review. RESULTS: Menstrual cycle length varied from 22 to 37 days (median 27 days). Ovulation by ultrasound ranged from day 8 to day 26 (median day 15). Serum and urinary hormone profiles showed excellent agreement. Estrogen and LH hormone peaks in urine and serum showed a range of signal characteristics across the study group before and after ovulation. The rise in estrogen and LH always occurred before ovulation; the progesterone rise from baseline always occurred after ovulation. CONCLUSIONS: Urinary and serum reproductive hormones showed excellent agreement and may be used interchangeably. The beginning of the surge in serum and urinary LH was an excellent predictor of ovulation. The rise in progesterone and P3G above baseline was a consistent marker of luteinisation confirming ovulation. Both LH and progesterone surges delivered clear, sharp signals in all volunteers, allowing reliable detection and confirmation of ovulation.

Characterization of follicle stimulating hormone profiles in normal ovulating women.

OBJECTIVE: To describe FSH profile variants. DESIGN: Observational study. SETTING: Multicenter collaborative study. PATIENT(S): A total of 107 women. INTERVENTION(S): Women collected daily first morning urine and underwent serial ovarian ultrasound. MAIN OUTCOME MEASURE(S) FSH RESULT(S): The individual FSH cyclic profiles demonstrated a significant departure from the currently accepted model. A decline in FSH levels at the end of the follicular phase was observed in only 42% of cycles. The absence of this decline was significantly associated with a shorter luteal phase and higher pregnanediol-3α-glucuronide, FSH, and LH levels at the time of ovulation. In 34% of the cycles, significant FSH variability was observed throughout the follicular phase; this variability was associated with higher body mass index and lower overall FSH and LH levels throughout the cycle. The FSH peak occurs on average 2 hours before ovulation. The FSH peak duration was shorter than the LH peak. CONCLUSION(S): These results suggest that average FSH profiles may not reflect the more complex dynamics of daily hormonal variations in the menstrual cycle. It is possible that discrepancies between the average normal FSH profile and the individual day-to-day variants can be used to detect abnormalities.

Use of urinary pregnanediol 3-glucuronide to confirm ovulation.

OBJECTIVE: Urinary hormonal markers may assist in increasing the efficacy of Fertility Awareness Based Methods (FABM). This study uses urinary pregnanediol-3a-glucuronide (PDG) testing to more accurately identify the infertile phase of the menstrual cycle in the setting of FABM. METHODS: Secondary analysis of an observational and simulation study, multicentre, European study. The study includes 107 women and tracks daily first morning urine (FMU), observed the changes in cervical mucus discharge, and ultrasonography to identify the day of ovulation over 326 menstrual cycles. The following three scenarios were tested: (A) use of the daily pregnandiol-3a-glucuronide (PDG) test alone; (B) use of the PDG test after the first positive urine luteinizing hormone (LH) kit result; (C) use of the PDG test after the disappearance of fertile type mucus. Two models were used: (1) one day of PDG positivity; or (2) waiting for three days of PDG positivity before declaring infertility. RESULTS: After the first positivity of a LH test or the end of fertile mucus, three consecutive days of PDG testing over a threshold of 5µg/mL resulted in a 100% specificity for ovulation confirmation. They were respectively associated an identification of an average of 6.1 and 7.6 recognized infertile days. CONCLUSIONS: The results demonstrate a clinical scenario with 100% specificity for ovulation confirmation and provide the theoretical background for a future development of a competitive lateral flow assay for the detection of PDG in the urine.

Relationships between the luteinizing hormone surge and other characteristics of the menstrual cycle in normally ovulating women.

OBJECTIVE: To describe the LH surge variants in ovulating women and analyze their relationship with the day of ovulation and other hormone levels. DESIGN: Secondary analysis of a prospective cohort observational study. SETTING: Eight natural family planning clinics. SUBJECTS: Normally fertile women (n = 107) over 283 cycles. INTERVENTION(S): Women collected daily first morning urine, charted basal body temperature and cervical mucus discharge, and underwent serial ovarian ultrasound. MAIN OUTCOME MEASURE(S): Urinary LH, FSH, estrone-3-glucuronide (E3G), pregnanediol-3α-glucuronide (PDG), and day of ovulation by ultrasound (US-DO). RESULT(S): Individual LH surges were extremely variable in configuration, amplitude, and duration. The study also showed that LH surges marked by several peaks were associated with statistically significant smaller follicle sizes before rupture and lower LH level on the day of ovulation. LH surges lasting >3 days after ovulation were associated with a lower E3G before ovulation, a smaller corpus luteum 2 days after ovulation, and a lower PDG value during the first 4 days after ovulation. CONCLUSION(S): In clinical practice, LH profiles should be compared with the range of profiles observed in normally fertile cycles, not with the mean profile.

Peripheral oxytocin in female baboons relates to estrous state and maintenance of sexual consortships.

The neuro-hypophysial hormone oxytocin (OT) has been implicated in female reproductive and maternal behaviors and in the formation of pair bonds in monogamous species. Here we measure variation in urinary OT concentrations in relation to reproductive biology and socio-sexual behavior in a promiscuously breeding species, the chacma baboon (Papio hamadryas ursinus). Subjects were members of a habituated group of baboons in the Okavango Delta, Botswana. We collected behavioral data and urine samples from n=13 cycling females across their estrous cycles and during and outside short-term, exclusive sexual consortships. Samples were analyzed via enzyme immunoassay (EIA) and we used linear mixed models (LMM) to explore the relationship between peripheral OT and a female's estrous stage and consortship status, her previous reproductive experience and fertility. We also used a Pearson's correlation to examine the relationship between OT concentrations of consorting females and their extent of behavioral coordination with their consort partners. The results of the LMM indicate that only estrous stage had a significant influence on OT levels. Females had higher OT levels during their periovulatory period than during other stages of their estrous cycle. There were no differences in the OT levels between consorting and non-consorting periovulatory females. However, among consorting females, there was a significant positive relationship between urinary OT levels and the maintenance of close proximity between consort partners. Our results suggest that physiological and behavioral changes associated with the initiation and maintenance of short-term inter-sexual relationships in baboons correspond with changes in peripheral OT.

Monitoring of ovarian activity by measurement of urinary excretion rates of estrone glucuronide and pregnanediol glucuronide using the Ovarian Monitor, Part II: reliability of home testing.

BACKGROUND: The UNDP/WHO/World Bank/Special Programme of Research, Development and Research Training in Human Reproduction (Geneva) set up a study to determine whether it is feasible for women to monitor their ovarian activity reliably by home testing. Daily self-monitoring of urinary hormone metabolites for menstrual cycle assessment was evaluated by comparison of results obtained with the Home Ovarian Monitor by untrained users both at home and in study centres. METHODS: Women collected daily data for urinary estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) for two cycles, then the procedure was repeated in the women's local centre (in Chile, Australia or New Zealand) giving a total of 113 duplicate cycles. The tests were performed without the benefit of replicates or quality controls. The home and centre cycles were normalized and compared to identify assay errors, and the resulting home and centre menstrual cycle profiles were averaged. RESULTS: Reliable mean cycle profiles were obtained with the home and centre excretion rates agreeing to within 36 ± 21 nmol/24 h for E1G and 0.77 ± 0.28 µmol/24 h for baseline PdG values (1-5 µmol/24 h). The cycles had a mean length of 28.1 ± 3.1 days (n = 112; 5th and 95th percentiles: 24 and 35 days, respectively), a mean follicular phase of 14.8 ± 3.1 days (n = 107; 5th and 95th percentiles: 11 and 21 days) and a mean luteal phase length of 13.3 ± 1.5 days (n = 106; 5th and 95th percentiles: 11 and 17 days), calculated from the day of the LH peak. CONCLUSIONS: The study confirmed that the Ovarian Monitor pre-coated assay tubes worked well even in the hands of lay users, without standard curves, quality controls or replicates. Point-of-care monitoring to give reliable fertility data is feasible.

Conception probabilities at different days of menstrual cycle in Chinese women.

OBJECTIVE: To investigate the conception probability among Chinese women. DESIGN: Prospective observational study. SETTING: Clinics in hospitals and family planning institutes in 10 provinces and cities. PATIENT(S): A total of 851 healthy married women aged 18-35 years with normal menstrual cycles who wish to have babies and with no contraception. INTERVENTION(S): Urinary LH was measured around days of expected ovulation for 7 days. The Barrett and Marshall model was used for calculation of conception probabilities on each cycle day from day -5 to day +1 in women with multiple episodes of intercourse. MAIN OUTCOME MEASURE(S): Pregnancies in 1, 3, and >or=6 months. RESULT(S): A total of 851 women with 2,055 cycles were analyzed. In 489 cycles there was only one episode of intercourse. A total of 601 pregnancies occurred. The conception probabilities from days in relation to ovulation -5 to +1 for a single episode of intercourse were 0.216, 0.102, 0.236, 0.233, 0.388, 0.293, and 0.386, respectively, and for multiple episodes they were 0.254, 0.271, 0.293, 0.365, 0.315, and 0.284, respectively, with the peak value at day -1. Recalculation of the efficacy of emergency contraception with low-dose mifepristone with the present conception probabilities showed higher efficacy. CONCLUSION(S): Conception probabilities among Chinese women are different from those in the literature. Further comparative studies are needed to confirm an ethnic difference.

Production of human chorionic gonadotropin during the normal menstrual cycle.

OBJECTIVE: To present a comprehensive study of pituitary human chorionic gonadotropin (hCG) production during the menstrual cycle, investigating its occurrence, timing and the possibility of a separate biologic role for pituitary hCG during the normal menstrual cycle. STUDY DESIGN: Daily urine samples were tested from 185 women during 405 normal menstrual cycles. Levels of hCG and luteinizing hormone (LH) were measured daily. RESULTS: hCG levels were detected at LH peak in 84% of menstrual cycles. At this time, hCG levels paralleled LH values. The remaining menstrual cycles (16%) had significantly lower LH levels, suggesting lack of detection of hCG as a result of low concentration of LH or very dilute urines. We infer that hCG is produced in all menstrual cycles. CONCLUSION: hCG is seemingly produced alongside LH in all menstrual cycles. hCG has a much greater circulating half-life compared to LH. It may function to extend the short, sharp LH peak in promoting ovulation or in promoting initial progesterone production by the corpus luteal cells.

Partial recovery of luteal function after bariatric surgery in obese women.

OBJECTIVE: To determine whether obesity-related reproductive endocrine abnormalities in ovulatory women are reversible with weight loss. DESIGN: Observational cohort study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Women aged 18-48 years with regular menstrual cycles 21-40 days and a body mass index (BMI) >or=35 kg/m(2) planning to undergo bariatric surgery were recruited. INTERVENTION(S): Twenty-five eumenorrheic (non-polycystic ovary syndrome) women with a mean BMI of 47.3 +/- 5.2 kg/m(2) were sampled with daily menstrual cycle urinary hormones before (n = 25) and 6 months after (n = 9) weight loss surgery resulting in >25% reduction of initial body weight. Daily hormones were compared before and after surgery and with 14 normal-weight control subjects. MAIN OUTCOME MEASURE(S): Metabolites of LH, FSH, E(2), and P were measured daily for one menstrual cycle. Group means were compared using t tests among ovulatory cycles. RESULT(S): Luteal pregnanediol glucuronide (Pdg) increased from 32.8 +/- 10.9 to 73.7 +/- 30.5 microg/mg creatinine (Cr) and whole-cycle LH increased from 168.8 +/- 24.2 to 292.1 +/- 79.6 mIU/mg Cr after surgically induced weight loss. Luteal Pdg remained lower than in normal-weight control subjects (151.7 +/- 111.1 microg/mg Cr). Obese women took longer to attain a postovulatory Pdg rise of >2 microg/mg Cr than control subjects (3.91 +/- 1.51 vs. 1.71 +/- 1.59 days); this improved after surgery (2.4 +/- 1.82 days). Whole-cycle estrone conjugates (E(1c)) was similar to control subjects at baseline, but decreased after weight loss (from 1,026.7 +/- 194.2 to 605.4 +/- 167.1 ng/mg Cr). Follicle-stimulating hormone did not relate to body size in this sample. CONCLUSION(S): Women of very high BMI have deficient luteal LH and Pdg excretion and a delayed ovulatory Pdg rise compared with normal-weight women. Although these parameters improved with weight loss, Pdg did not approach levels seen in normal-weight women. Luteinizing hormone may be less effective in stimulating the corpus luteum in obesity. The large postoperative decrease in E(1c) may reflect the loss of estrone-producing adipose tissue after weight loss.