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The effect of goat nutritional condition on the response to biostimulation with sexually active males during different stages of anestrus was determined. Fifty-eight Criollo × Nubian females on high and low body mass index (BMI) diets were used. Each BMI group was divided into two for biostimulation with sexually active males during May (mid-anestrus) or July (transition period). Ovulatory responses to biostimulation were characterized from serum progesterone, as well as the delay for response (first and second ovulations followed by a normal length luteal phase, O-WNLP). The percentage of goats showing one O-WNLP was greater in the high BMI group than in the low BMI group and greater during the transition period than in the mid-anestrus. However, the interaction between factors revealed that the difference between BMI groups was only significant in the transition period and the difference between stages was only significant in goats with high BMI. Occurrence of a second O-WNLP tended to be greater in the high BMI group than in the low BMI group. Response delay was shorter in the transition period than in mid-anestrus. In conclusion, female nutritional status interacting with the stage of anestrus determined the ovulatory response to male biostimulation in crossbred Criollo goats., (© 2016 Japanese Society of Animal Science.)

Objective: To study the role of micro-RNA (miRNA)-200b and miRNA-429 in human ovulation and to measure their expression levels in ovulatory and anovulatory patients., Design: Micro-RNA-200b and miRNA-429 expression analysis in human serum and granulosa cells at different phases of the ovulation cycle in normal cycling women and women undergoing assisted reproductive technology cycles., Setting: University-affiliated hospital and academic research laboratory., Patient(s): Forty women (7 normally ovulating, 15 normally ovulating with pure male infertility factor, and 18 with polycystic ovary syndrome) were included in this study., Intervention(s): None., Main Outcome Measure(s): The expression profile of circulating miRNAs and granulosa cells was assessed by means of real-time quantitative reverse transcription-polymerase chain reaction analysis., Result(s): We identified miRNA-200b and miRNA-429 in the sera of all women tested. These miRNA expression levels were elevated during the early follicular phase of the cycle compared with serum levels during the early luteal phase. Anovulatory women, diagnosed with polycystic ovary syndrome, expressed significantly higher levels of miRNA-200b and miRNA-429 compared with spontaneously ovulating women. Ovulation induction with exogenous gonadotropins during an IVF cycle reduced these levels to the levels measured in normal ovulating women., Conclusion(s): Our findings suggest an involvement of miRNA-200b and miRNA-429 in the pituitary regulation of human ovulation. Although it is unclear whether this altered miRNA expression profile is a cause or a result of anovulation, the levels of these molecules in the serum of anovulatory women may serve as serum biomarkers for the ovulation process., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Blood flow to uterus and ovaries is demonstrated to be altered during mensturation. Studies has been published stating that blood flow differs also in ovulatory and anovulatory cycles. In this study, using color Doppler ultrasound, we aim to compare uterine, endometrial and ovarian blood flow during ovulatory and anovulatory cycles., Material and Methods: Women volunteers who are aged between 18-40 had no endocrinological problem and not recieving exogenous hormone therapy were included to study. Blood levels of FSH, LH, E2, prolactine, DHEAS, free T4 were collected in early follicular phase. Uterina, subendometrial and intraovarian artery blood flow pulsatility and resistance indexes were analysed using Doppler USG technique. Patients were called out to control on 21st of cycle and progesterone levels were analysed. Patients who has ovulation signs in USG and progesterone level above 5 ng/mL were included to ovulatory cycle group. Patient who has no signs of ovulation in ultrasound and has not enough progesterone level were included to anovulatory cycle group., Results: LH and E2 levels were significantly higher in anovulatory patients. No correlation was found between endometrial blood flow resistance and basal E2, prolactine, testosterone levels. However, DHEAS levels were related to endometrial blood flow resistance in anovulatory cycles. No correlation was found between ovarian blood flow resistance/uterine blood flow resistance and basal E2, prolactine, testosterone, DHEAS levels., Conclusions: There is statistically significant difference between endometrial, ovarian, uterine artery blood flow resistance in ovulatory and anovulatory cycles. Blood flow resistance was found to be increased in anovulatory patients. Increased E2 levels in anovulatory cycles were related to endometrial linethickness and endometrial volume.

Objective: This study aims to test the hypothesis that consistently ovulatory premenopausal/perimenopausal women have a more favorable cardiometabolic profile than anovulatory women., Methods: The first four collections from the Study of Women's Health Across the Nation Daily Hormone Study (DHS) were used. DHS enrollees annually completed a daily collection of first morning voided urine for an entire menstrual cycle or up to 50 days (whichever comes first). A woman was categorized as consistently ovulatory annually (COA) if four ovulatory cycles or two to three ovulatory cycles followed by the final menstrual period (FMP) were observed. A woman was categorized as not consistently ovulatory annually (nCOA) if at least one anovulatory year was observed. Cross-sectional and longitudinal differences were compared between COA and nCOA women. Data were centered at FMP and adjusted for age and body mass index (BMI)., Results: Six hundred thirty-six DHS participants (mean [SD] age, 47.3 [2.5] y; mean [SD] BMI, 27.4 [7.1] kg/m(2)) were included. Thirty-six percent of the DHS participants were COA women. On the fourth follow-up collection, COA women had lower high-density lipoprotein than nCOA women (mean [95% CI], 55.7 [54.0-57.4] vs 59.5 [57.9-61.0] mg/dL, P = 0.002, respectively), which persisted after adjustment. Among 460 women with FMP, 39% were COA women. COA women were slightly older (52.9 vs 52.0 y, P = 0.002) and had lower BMI (geometric mean, 26.1 vs 27.5 kg/m(2), P = 0.06) than nCOA women at FMP. Other cardiometabolic factors did not significantly differ by COA status through FMP., Conclusions: Consistent ovulation across the menopausal transition does not seem to reflect superior cardiometabolic health.

Objective: To compare previously used algorithms to identify anovulatory menstrual cycles in women self-reporting regular menses., Design: Prospective cohort study., Setting: Western New York., Patient(s): Two hundred fifty-nine healthy, regularly menstruating women followed for one (n=9) or two (n=250) menstrual cycles (2005-2007)., Intervention(s): None., Main Outcome Measure(s): Prevalence of sporadic anovulatory cycles identified using 11 previously defined algorithms that use E2, P, and LH concentrations., Result(s): Algorithms based on serum LH, E2, and P levels detected a prevalence of anovulation across the study period of 5.5%-12.8% (concordant classification for 91.7%-97.4% of cycles). The prevalence of anovulatory cycles varied from 3.4% to 18.6% using algorithms based on urinary LH alone or with the primary E2 metabolite, estrone-3-glucuronide, levels., Conclusion(s): The prevalence of anovulatory cycles among healthy women varied by algorithm. Mid-cycle LH surge urine-based algorithms used in over-the-counter fertility monitors tended to classify a higher proportion of anovulatory cycles compared with luteal-phase P serum-based algorithms. Our study demonstrates that algorithms based on the LH surge, or in conjunction with estrone-3-glucuronide, potentially estimate a higher percentage of anovulatory episodes. Addition of measurements of postovulatory serum P or urine pregnanediol may aid in detecting ovulation., (Published by Elsevier Inc.)

We investigated whether sexual activity was associated with reproductive function in the BioCycle Study, a prospective cohort study that followed 259 regularly menstruating women aged 18 to 44years for one (n=9) or two (n=250) menstrual cycles in 2005-2007. Women were not attempting pregnancy nor using hormonal contraceptives. History of ever having been sexually active was assessed at baseline and frequency of sexual activity, defined as vaginal-penile intercourse, was self-reported daily throughout the study. Serum concentrations of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, and testosterone were measured up to 8times/cycle. Sporadic anovulation was identified using peak progesterone concentration. Linear mixed models were used to estimate associations between sexual activity and reproductive hormone concentrations and generalized linear models were used to estimate associations with sporadic anovulation. Models were adjusted for age, race, body mass index, perceived stress, and alcohol consumption and accounted for repeated measures within women. Elevated concentrations of estrogen (+14.6%, P<.01), luteal progesterone (+41.0%, P<.01) and mid-cycle LH (+23.4%, P<.01), but not FSH (P=.33) or testosterone (P=.37), were observed in sexually active women compared with sexually inactive women (no prior and no study-period sexual activity); sexually active women had lower odds of sporadic anovulation (adjusted odds ratio=0.34, 95% confidence interval: 0.16-0.73). Among sexually active women, frequency of sexual activity was not associated with hormones or sporadic anovulation (all P>.23). Findings from our study suggest that ever having been sexually active is associated with improved reproductive function, even after controlling for factors such as age., (Published by Elsevier Inc.)

Background: Because of the substantial energy demands of reproduction, the brain must temper the fertility of individuals to match nutritional availability. Under-nutrition is associated with infertility in humans and animals. The brain uses adipose- and gut-derived hormones, such as leptin, insulin and ghrelin, to modulate the activity of the GnRH neuronal network that drives reproduction. It is becoming clear that there are both direct and indirect pathways acting on GnRH neurones., Methods: A PubMed search was performed using keywords associated with neuropeptides and metabolic hormones that are associated with reproductive and energy balance axes., Results: Evidence that neurones which produce galanin, galanin-like peptide, kisspeptin, alpha-melanocyte-stimulating hormone, neuropeptide Y and oxytocin convey metabolic information to the reproductive axis is presented. The extent to which these neurones express receptors for metabolic hormones is variable but interactions between them allows for complex intermingling of information. Available metabolic fuels modulate hormone input to these neurones, leading in turn to altered GnRH release and appropriate drive to the gonads. The consequent change in sex steroid production is likely to contribute to co-ordination of the network., Conclusions: We hypothesize that the absence of an estrogenic milieu during anovulation compared with presence of estradiol during follicular maturation is important for the regulation of most of the neuropeptides. An improved understanding of the normal responses to energy deprivation may also help to identify novel therapeutic targets for infertility that often accompanies metabolic disorders, such as diabetes, obesity and polycystic ovary syndrome.

Purpose: To determine if seizure frequency differs between anovulatory and ovulatory cycles., Methods: The data came from the 3-month baseline phase of an investigation of progesterone therapy for intractable focal onset seizures. Of 462 women who enrolled, 281 completed the 3-month baseline phase and 92 had both anovulatory and ovulatory cycles during the baseline phase. Midluteal progesterone levels ≥5 ng/ml were used to designate cycles as ovulatory. Among the 92 women, average daily seizure frequency (ADSF) for all seizures combined and each type of seizure considered separately (secondary generalized tonic-clonic seizures - 2°GTCS, complex partial seizures - CPS, simple partial seizures - SPS) were compared between anovulatory and ovulatory cycles using paired t-tests. A relationship between the proportional differences in ADSF and estradiol/progesterone (EP) serum level ratios between anovulatory and ovulatory cycles was determined using bivariate correlational analysis., Key Findings: ADSF was 29.5% greater for 2°GTCS during anovulatory than during ovulatory cycles. ADSF did not differ significantly for CPS or SPS or for all seizures combined. Proportional differences in anovulatory/ovulatory 2°GTCS ADSF ratios correlated significantly with differences in anovulatory/ovulatory EP ratios. Among the 281 women, the three seizure types did not differ in ovulatory rates, but EP ratios were greater for cycles with 2°GTCS than partial seizures only., Significance: Seizure frequency is significantly greater for 2°GTCS, but not CPS or SPS, during anovulatory cycles than ovulatory cycles. Because the proportional increases in 2°GTCS frequency during anovulatory cycles correlate with the proportional increases in EP level ratios, these findings support a possible role for reproductive steroids in 2°GTCS occurrence., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Central fat distribution is increased in anovulatory women with polycystic ovary syndrome (PCOS) compared with ovulatory PCOS and matched controls. Among secreted adipocytokines, this is reflected mainly in lower levels of adiponectin.

Objective: To determine the first-line medication to be used in anovulatory patients with polycystic ovary syndrome (PCOS) for ovulation induction and pregnancy achievement., Design: Randomized controlled trial., Setting: Infertility unit of a public hospital., Patient(s): One hundred fifteen newly diagnosed patients with PCOS based on ESHRE/ASRM criteria., Intervention(s): These patients were assigned to three groups: group 1 (38 patients) received 500 mg of metformin three times a day; group 2 (39 patients) received clomiphene citrate (CC) at an incremental dose; group 3 (38 patients) received both medications., Main Outcome Measure(s): Rates of ovulation, pregnancy (PR), and live birth., Result(s): The ovulation rate was 23.7% in the metformin group, 59% in the CC group, and 68.4% in the combination treatment group. This was translated into a similar PR and live birth rate, which were higher in the CC and combination groups compared to the metformin group (PR: 7.9%, 15.4%, and 21.1%; live birth rate: 7.9%, 15.4%, and 18.4% in metformin, CC, and combination treatment groups, respectively), although statistically the differences were not significant. There were no multiple pregnancies and the rate of spontaneous first trimester loss was similar to the general population., Conclusion(s): Clomiphene citrate should be the first-line treatment for ovulation induction in anovulatory patients with PCOS.

The present paper describes LH and FSH secretion, follicle development and ovulation in sows that were subjected to a limited nursing regimen. From Day 14 of lactation, 32 sows were separated from their piglets for 12 h every day (intermittent suckling; IS). Half the sows had boar contact during separation. Nine of 32 sows ovulated spontaneously within 14 days from initiation of IS. The frequency of LH pulses on the first day of IS tended to be higher in anovulatory sows (6.3 v. 4.2 pulses per 12 h; P < 0.10); other characteristics of LH secretion were similar to sows that ovulated. The characteristics of FSH secretion did not differ over the 8-h sampling period. Boar contact did not influence either LH and FSH secretion or the number of sows that ovulated. Up to 58% of anovulatory sows showed an increase in follicle size after initiation of IS and, 4 days after the initiation of IS, one-third still had follicles similar in size to those in ovulatory sows. However, the oestradiol concentration in anovulatory sows did not increase. We conclude that FSH and LH stimulation in anovulatory sows is not limiting for normal follicle development, but that ovarian follicles are not responsive to increased LH secretion.

Background/aim: Any organs functioning directly depends on vascularization. It applies also to the uterus and ovary which go through changes of vascularization during a menstruation cycle. The aim of this investigation was to determine differences in intrauterine and ovarian stromal arterioral blood flow on basal ultrasound examination (day 2-4) between spontaneous ovulatory and anovulatory cycles., Methods: This prospective clinical investigation included 205 patients divided into two groups: with ovulatory and with anovulatory cycles., Results: Resistance to ovarian arterioral stromal blood flow was significantly lower in the patients with ovulatory cycles (pulsatile index--PI 0.97 +/- 0.4 vs 1.93 +/- 1.37; p = 0.001737; and (resistance index - RI 0.55 +/- 0.12 vs 0.68 +/- 0.14; p = 0.040033). There. were no statistically significant differences in arcuate arterioral blood flow in the pateints with ovulatory and anovulatory cycles (PI 1.21 +/- 0.34 vs 61 +/- 0,61 p = 0.136161 and RI 0.64 +/- 0.11 vs 0.74 +/- 0.07; p = 0.136649). The patients with ovulatory cycles had lower uterine radial arterioral blood flow than the patients with anovulatory cycles (PI 1.001 +/- 0.22 vs 1.61 +/- 0.23 p = 0.007501 and RI 0.55 +/- 0.08 vs 0.71 +/- 0.12; p = 0,0460113). The patients with ovulatory cycles had lower subendometrial arterioral blood flow resistance (PI 0.69 0.19 vs 1.385 +/- 0.09; p = 0.00622 and RI 0.44 +/- 0.09 vs 0.65 +/- 0.02; p = 0.027458)., Conclusion: Color Doppler ultrasuond imaging and measurements of intrauterine and ovarian stromal arterioral blood flow on basal ultrasound examination (day 2-4), showed lower resistance to blood flow in ovulatory than in anovulatory cycles.

Objective: To examine whether use of multivitamins and intake of specific nutrients in multivitamins is associated with ovulatory infertility., Design: A prospective cohort study., Setting: The Nurses' Health Study II., Patient(s): Eighteen thousand five hundred fifty-five married, premenopausal women without a history of infertility who attempted a pregnancy or became pregnant between 1991 and 1999., Intervention(s): None, observational study., Main Outcome Measure(s): Incident reports of infertility caused by anovulation., Result(s): During 8 years of follow-up, 438 women reported infertility caused by ovulatory disorder. There was an inverse association between frequency of multivitamin use and ovulatory infertility. The multivariate-adjusted relative risk (95% confidence interval) of ovulatory infertility was 0.88 (0.60, 1.28) for women consuming two tablets per week or less, 0.69 (0.51, 0.95) for women consuming three to five tablets per week, and 0.59 (0.46, 0.75) for women consuming six or more tablets per week, when compared with women who did not use these supplements (P, trend <.001). Folic acid appeared to explain part of the association between multivitamin supplement use and risk of ovulatory infertility., Conclusion(s): Regular use of multivitamin supplements may decrease the risk of ovulatory infertility.

Estrogens and progesterone represent the key ovarian hormones produced by the developing ovulatory follicle. Serum concentrations start to rise from the mid-follicular phase onwards, coinciding with the development of the dominant follicle. Androgens are converted into estrogens by aromatase activity of the granulosa cells and secreted into the follicular fluid compartment. Their significance for oocyte maturation and fertilizing potential remains unknown. Paradoxically, serum estrogen levels are within the normal range in the majority of patients presenting with cycle abnormalities due to ovarian dysfunction. Similarly, the distribution of estradiol (E2) and follicle-stimulating hormone (FSH) levels within the normal range is comparable between normo-ovulatory controls and normogonadotropic anovulatory women. Moreover, E2 levels are only moderately correlated with luteïnizing hormone (LH), testosterone (T), androstenedione (A), sex hormone binding globulin (SHBG), the free androgen index (FAI) and finally ovarian volume as measured by ultrasound. No correlations could be found between E2 and age, body weight and cycle history and FSH. Androgen concentrations and cycle history--but not E2--were the most prominent predictors of ovarian response tot the conventional ovulation induction. Anti-estrogenic compounds like clomiphene citrate and tamoxifen have remained the first-line treatment of choice for anovulation. Certainly, CC and to a lesser extent tamoxifen have demonstrated to exhibit undesired anti-estrogenic properties at the uterine level however. However, large follow-up studies demonstrate cumulative ovulation rates around 75%, and the overall pregnancy rates of around 50%. Aromatase inhibitors, another way to interfere with estrogen feedback, represent a feasible option. This claim should, however, be substantiated by further sufficiently powered, controlled studies, and the possibility of embryo toxicity remains a major concern. In retrospect, CC and tamoxifen represent the first generation of selective estrogen receptor modulators (SERMs), and many new compounds have recently been introduced into the clinic or are currently under investigation. The major focuses of these compounds are bone density, the cardiovascular system and breast cancer. No studies have been reported in the area of ovarian stimulation.

Anovulation, a common cause of female infertility, is a highly curable condition. Presented here is a simple treatment-orientated diagnostic scheme. Anovulatory women with low endogenous oestradiol and follicle stimulating hormone (FSH) are treated with either pulsatile gonadotrophin releasing hormone (GnRH) or gonadotropins, and women with eu-oestrogenic anovulation (mostly with polycystic ovarian syndrome; PCOS) have first-line treatment with clomiphene citrate (CC), possibly with metformin. If CC fails, FSH is administered using a chronic low-dose protocol with small incremental dose rises. A comparison of urinary with recombinant and pure FSH with luteinising hormone (LH) containing gonadotropins is made. Recombinant products are purer and more convenient for use but are expensive. LH content has little impact except in hypogonadotropic hypogonadism or severe pituitary suppression with GnRH analogues. Aromatase inhibitors, recombinant LH and long-acting FSH may find a future place in the armamentarium.

Mono-ovulatory cycles for women are optimal because singleton pregnancies have a better outcome than multiples. Multiple births began to increase in the 1950s after the first appearance of effective ovulation induction for the treatment of anovulation. Since the 1980s when ovulation induction and IVF were more broadly applied to the treatment of unexplained and persistent infertility, there has been an unprecedented rise in multiple births. Strategies to achieve mono-ovulation during treatment of anovulatory patients are distinct from those for the treatment of ovulating patients who have unexplained and persistent infertility. Anovulatory patients with hypogonadotrophic hypogonadism can be treated with exogenous pulsatile GnRH, which restores normal gonadotrophin secretion, ovulation rates and conception rates. The multiple pregnancy rate is not increased with GnRH treatment. In patients with normogonadotrophic anovulation, attention should be given to diet and exercise before any other interventions are considered. Pharmacological induction of ovulation can be achieved with antiestrogen, gonadotrophin or pulsatile GnRH treatment; antiestrogen is the first choice with gonadotrophin more widely used for clomiphene citrate (CC)-resistant patients. Obesity and polycystic ovaries are common in this group, so that gonadotrophin and GnRH treatment are associated with lower responses compared with hypogonadotrophic hypogonadism, and higher multiple pregnancy rates. Low dosage protocols are being tested that may lower the multiple birth rates. The role of drugs enhancing sensitivity to insulin, e.g. metformin, remains undetermined. Laparoscopic ovarian diathermy achieves conception rates that are equivalent to gonadotrophin treatment, with fewer multiple births. Augmenting normal ovulation processes for couples with unexplained and persistent infertility is less effective. Pregnancy rates are statistically significantly higher with CC but the size of the increase is not clinically important. CC with intrauterine insemination is associated with a clinically important effect on conception. Achieving mono-ovulation is more difficult in assisted reproductive technology cycles because success depends on maintaining the level of FSH above the threshold level longer than normal in order to increase the number of mature follicles. Milder stimulation for IVF and IVF in the untreated cycle show great potential, however, especially in view of the trend toward transfer of a single embryo in assisted reproductive treatment cycles.

Central nervous system pathways get influenced by the changing hormonal levels across the menstrual cycle. In an effort to see the effects on the conduction in central auditory pathways we recorded long latency auditory evoked potentials (LLAEPs) across the 4 different phases of the menstrual cycle. 20 females having normal ovulatory menstrual cycles were tested 4 times in a single cycle and LLAEPs were recorded from Cz-A1 and Cz-A2 position with alternating 90 dB sound pressure click stimuli. Twenty age matched control females having anovulatory menstrual cycles were also tested on the corresponding days. All control females were taking oral contraceptive (O.C.) pills. The LLAEPs were compared inter-group wise as well as inter-phase wise for each parameter by using hierarchal ANOVA design and Tukey test was applied to find out the significance level. Peak latencies of waves P2 and N2 were found to be delayed during mid-cycle and relatively reduced mid-luteal phase in ovulatory menstrual cycles. No such response was noticed in oral contraceptive using group. This indicates that normal cyclic variations of female sex hormones especially estrogen and progesterone modify the central processing of the auditory information. Estrogen may be responsible for delaying the conduction by influencing GABA release at the level of polysensory association areas of the brain.

Article abstract-- In an investigation of 100 women with localization-related epilepsy, anovulatory cycles were significantly greater in proportion in women with 21-25 or 33-35 day cycles (Group B) and in women with less than 21 or more than 35 day cycles (Group C) than in women with normal 26-32 day intervals (Group A). Groups B and C also had significantly higher estradiol/progesterone ratios than Group A. Nevertheless, almost one-half (46.2%) of the anovulatory cycles occurred in women with normal 26-32 day cycles.

In nonobese girls with an adolescent variant of polycystic ovary syndrome, insulin-sensitizing treatment reduces hyperinsulinism, dyslipidemia, and hyperandrogenism and restores eumenorrhea; however, the effect on anovulation is unknown. We assessed whether metformin treatment is capable of inducing ovulation in nonobese adolescents with anovulatory hyperandrogenism after precocious pubarche. The study population consisted of 18 adolescents (mean age, 16 yr; body mass index, 21.4 kg/m2; 3-7 yr beyond menarche) with hyperinsulinemic hyperandrogenism. All girls received metformin for 6 months in a daily dose of 1275 mg. Before inclusion, persistent anovulation was documented by weekly serum progesterone measurements less than 4 ng/ml (months -3 and -1); the ovulation rate was assessed similarly after 2, 4 and 6 months on metformin; a premenstrual progesterone level greater than 8 ng/ml was used as ovulation marker. Regular menses were reported by 16 of 18 girls within 4 months on metformin, and all girls were eumenorrheic after 6 months on metformin. Of the 18 girls, 1 (6%) ovulated after 2 months on metformin, 7 (39%) after 4 months, and 14 (78%) after 6 months; ovulation induction failed in the girls with the lowest birth weight or most severe hyperandrogenism. Metformin treatment was well tolerated. In conclusion, sensitization to insulin was found to be an effective approach to induce ovulation in nonobese adolescents with anovulatory hyperandrogenism.

Background: Oligomenorrhea, defined as a menstrual cycle lasting 36 to 90 days, can be a normal condition in the first years after the menarche. When it persists or appears after a period of normal menstrual cycles, an underlying illness must be sought., Aim: To assess ovulation and causes of anovulatory cycles in women with oligomenorrhea, compared with causes of secondary amenorrhea., Patients and Methods: One hundred one women of less the 35 years old, presenting with oligomenorrhea persisting 5 years after menarche or lasting more than two years after a period of normal menstrual cycles, were studied. Ovulation was studied measuring serial plasma progesterone during normal or induced (with intramuscular progesterone) menstrual cycles., Results: Eighty nine percent of women had anovulatory oligomenorrhea. The main causes were polycystic ovarian disease in 51% and hypothalamic dysfunction in 31%. Thirty percent of women with secondary amenorrhea had polycystic ovarian disease and 14% had hyperprolactinemia. Women older than 20 years old or with more than 10 years of gynecological age had a higher frequency of polycystic ovarian disease and a lower prevalence of hypothalamic dysfunction., Conclusions: There is a high frequency of anovulatory oligomenorrheas. Therefore, this symptom deserves a thorough endocrinological assessment to uncover underlying diseases. Special attention must be paid to polycystic ovary syndrome, due to its importance in internal medicine as a risk factor for myocardial infarction, high blood pressure, and type 2 diabetes mellitus.

The case histories of three young women with ankylosing spondylitis, rheumatoid arthritis and a seronegative inflammatory polyarthritis undergoing investigations for infertility are presented. In each, non-steroidal anti-inflammatory drug (NSAID) therapy was associated with the recurrent development of luteinized unruptured ovarian follicles and normal ovulation following drug withdrawal. It is suggested that NSAID therapy may be an important and frequently overlooked cause of anovulation and infertility.

The results of histological examination of the endometrium are normal in most patients with unexplained sterility. Cathepsin D is a ubiquitous lysosomal protease regulated by progesterone in the endometrium. Assays of concentrations of cathepsin D might be useful in determining the functional responses of the endometrium to progesterone. To examine this possibility, we quantified immunostaining of endometrial cathepsin D using an image analysis system in women with regular menstrual cycles. An endometrial sample was obtained during the proliferative and luteal phases from 17 women with ovulatory menstrual cycles and at the beginning and during the last 14 days of a cycle from 15 women having anovulatory menstrual cycles. In endometrial glands of ovulatory women, cathepsin D protein immunostaining increased during the cycle and was significantly higher during the luteal than during the proliferative phase [51 +/- 38.1 arbitrary units (AU) versus 118.2 +/- 58.9 AU; P < 0.01]. This increase was also observed in stromal cells, although to a lesser extent (28.6 +/- 26.9 versus 41.5 +/- 43.1 AU; P = NS). In the endometrium of women with anovulatory menstrual cycles, cathepsin D staining was high both for the proliferative and the luteal biopsies in glands (respectively 95 +/- 43 and 104 +/- 51.3 AU) and stromal cells (respectively 61.8 +/- 33.8 and 75 +/- 32.6 AU). In women with ovulatory cycles, cathepsin D staining was localized in the apical part of glandular cells during the proliferative phase and diffused throughout the cytoplasm during the luteal phase. In contrast, in women with anovulatory cycles, cellular localization of cathepsin D remained apical in glands, regardless of the day of biopsy. In conclusion, this study shows that the cytoplasmic localization of cathepsin D might be a qualitative biological indicator of endometrial gland responses to progesterone. This could be a useful tool for evaluating cell function, which is poorly tested by histology alone.

Women with epilepsy have lower fertility rates than women without epilepsy. We hypothesized that limbic dysfunction in temporal lobe epilepsy (TLE) alters the release of hypothalamic trophic hormones that secondarily affect release of the pituitary gonadotropins, causing ovulatory failure. We assessed ovulatory function over three consecutive menstrual cycles in 17 women with partial seizures arising from the temporal lobe (TLE), 7 women with primary generalized epilepsy (PGE), and 12 controls. We devised scores to reflect ovulatory function that were based on daily basal body temperature and monthly serum progesterone levels. Seizure frequency, antiepileptic drugs (AEDs), and depressive symptomatology were also evaluated. Anovulation was more frequent in subjects with TLE (35.3%) than in subjects with PGE (0%) or in controls (8.3%). Anovulatory cycles tended to occur more frequently in subjects with TLE who were treated with polytherapy than in those receiving monotherapy, but this result was not statistically significant. Seizure frequency and symptoms of depression did not affect ovulatory function. Although AED polytherapy may increase the likelihood of anovulation, our results suggest a mechanism of infertility related to temporal lobe dysfunction.

Ovulatory cycles in women result from sequential stimulation of ovarian follicular development by pituitary follicle stimulating hormone (FSH) and luteinizing hormone (LH). In the follicular phase the initial FSH stimulus declines and LH secretion increases toward the mid-cycle ovulatory surge. During the luteal phase gonadotrophin secretion is reduced. This reflects the effects of ovarian steroids inhibiting the frequency of gonadotrophin releasing hormone (GnRH) secretion by the hypothalamus, and the direct effects of oestradiol and inhibin to reduce gonadotroph (FSH) secretion. The frequency of GnRH stimulation of the gonadotroph is a selective regulator of gonadotrophin synthesis, with slow frequency stimuli favouring FSH and faster frequency stimuli favouring LH secretion. Current research has only revealed a single gonadotrophin releasing hormone. Thus, the ability to change the pattern (particularly frequency) of GnRH stimulation of the gonadotroph is proposed as an important regulator of differential FSH and LH synthesis, and hence of ovulatory cycles. In some disorders of ovulation the ability to regulate GnRH pulse frequency appears to have been lost. Slow frequency GnRH pulses are consistently seen in women with hypothalamic amenorrhoea and hyperprolactinaemia. The reduced GnRH secretion appears to reflect increased hypothalamic opiate tone and can be rapidly reversed with an opiate receptor blocker. Other disorders associated with anovulation show rapid frequency GnRH secretion, and polycystic ovarian syndrome (PCO) is commonly associated with fast-frequency, high-amplitude LH (GnRH) pulses. Such a GnRH stimulus would favour LH and androgen production and the failure of ovarian follicular maturation in PCO may reflect inappropriate sequential FSH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

The luteinized unruptured follicle syndrome (LUF) is diagnosed in different numbers of cycles and its place in sterility etiology still has to be established. This article reviews today's diagnostic possibilities, the occurrence of LUF in patients with different types of sterility, the etiology and therapeutic approaches.

In rats with 5 day reproductive cycles, 'anovulatory' cycles were induced by blockade of ovulation with sodium pentobarbitone injected at pro-oestrus. Such anovulatory cycles were characterized in the ovaries by gradual atresia of the large follicles present at the time of the injection and the growth of a new cohort destined for the next ovulation. In the vaginal smears, anovulatory cycles were indistinguishable from normal ovulatory cycles. The serum concentrations of progesterone remained at baseline levels during dioestrus of anovulatory cycles whereas increased concentrations of progesterone were observed during dioestrus of ovulatory cycles. It is concluded that the 'non-functional' corpora lutea of the cycle are the source of dioestrous progesterone. The length of anovulatory cycles after a single injection of pentobarbitone was 5 days despite the absence of any increase in progesterone concentrations during dioestrus. It is concluded that progesterone production during dioestrus plays no major role in the control of the duration of 5 day reproductive cycles.

The authors have analyzed the characteristics of menstrual cycles during the post-partum without breastfeeding, according to the nature of the first period. 172 women gave the thermal curve from childbirth to the first period. Among them, 118, 111, 98 and 54 women gave the self-observation data concerning, respectively, the first, second, third and the fourth cycle after the first period. They have noticed more short luteal phases and delays in ovulation after an anovulatory first period than after an ovulatory first period. The hormonal studies in the post-partum without breastfeeding seem not to explain the whole of these anomalies ascertained beyond twelve post-partum weeks. Most authors admit that the gonadotropin axis returns to a normal state within the fifth post-partum week. Because of the peculiar kinetics of follicle development, the ovary could be an important component of the "remnant effect of gestation", that is to say, of the delay of return to post-partum ovulation following the gestation state.

Clinical examinations including morphometry, mammography, x-ray examination of the cranium, ultrasonic examination of the small pelvic organs help detect the patients with hypogonadotropic amenorrhea and predict the efficacy of ovulation induction with menopausal gonadotropin. Women with a positive reaction to administration of progesterone and LH releasing factor make up the group most promising in respect of ovulation induction with menopausal gonadotropin.

A comparative assessment of variations in sex hormone levels and echographic parameters of fertile and infertile cycles was carried out in patients with gonadotrophic deficiency during pergonal induction of the ovulation. It was demonstrated that 83% of the infertile cycles were the first stimulation cycles. Basic differences were identified in the variation of sex hormone levels and echographic parameters of target organs between the fertile and infertile cycles. It is concluded that the first ovulation-induction course should be regarded as a preventive or preparatory one, where an optimum drug dosage is adjusted while the gonads and target organs are getting ready for the ovulation.

Circadian profile and responsiveness of prolactin to TRH administration were examined in 21 women with ovulatory disturbances. The data were analyzed with reference to the clinical effectiveness of bromocriptine administration. Resting levels of serum prolactin in the patients studied were lower than 25 ng/ml. 14 patients out of 16 cases (Group A) responded to bromocriptine, whose prolactin levels were more than 30 ng/ml during the night in the circadian studies. On the other hand, none of 5 patient (group B) responded to bromocriptine, whose prolactin levels were not more than 30 ng/ml during the night. Group A showed hyper-responsiveness of prolactin to TRH higher than that of Group B. These results suggested that 1) In euprolactinemic ovulatory disturbances there are cases with nocturnal hyperprolactinemia, whose prolactin levels are normal during the day time. These cases will be referred to as occult hyperprolactinemia. 2) Those with occult hyperprolactinemia show increased prolactin-secreting-capacity, which is able to be diagnosed by the hyper-responsiveness of prolactin to TRH administration. 3) The effectiveness of bromocriptine in treating euprolactinemic ovulatory disturbances is due to the suppressive effect of bromocriptine on the hyperprolactinemic states of occult hyperprolactinemia.

Life-table analysis was performed for the cumulative spontaneous pregnancy rate (CSPR) of 56 patients with oligomenorrhea and anovulatory cycles who had been treated with gonadotropin for ovulation induction between 1963 and 1985. Twenty-seven had at least one spontaneous pregnancy, giving rise to a CSPR of 66.4% (95% confidence limit [CL] 42.4% to 90.4%) at 115 months for the first spontaneous pregnancy, which is significantly lower than the cumulative induced pregnancy rate (CIPR) of 88.6% at 23 months for the first course of gonadotropin therapy (P less than 0.0001). This fertility potential was not affected by the baseline estrogen and follicle-stimulating hormone levels, diagnosis, result of gonadotropin therapy, and age and menstrual pattern during exposure to spontaneous pregnancy by Cox regression analysis. More multiple births occurred in the induced pregnancies than in the spontaneous pregnancies (P = 0.005).

The relation between ultrasonographic signs of ovulation and serum estradiol (E2) rise and luteinizing hormone (LH) surge were studied. Forty-eight cycles were examined in Twenty-eight infertile patients. The correlation between the follicular diameter as measured by ultrasound and actual follicular diameter under direct visualization was also determined in 19 follicles of the 25 patients who had undergone laparotomy. In 34 of the 48 cycles, growing follicles and follicular rupture could be observed by ultrasound (72.3%). The mean diameter of the follicles measured the day before estimated ovulation was 22.4 +/- 2.75 mm(range 16-27mm). The ultrasonographic ovulation period (UOP) occurred within 24 hours from the day of maximal LH levels in 24 of the 34 cycles, and within 48 hours from the day of the E2 peak in 25 of the 34 cycles. The follicular diameter measured by ultrasound was greater than the actual diameter found during laparotomy, but there was a high degree of correlation (r = 0.900). Furthermore, the E2 and P levels in follicular fluid were high in large follicles and correlated well with the ultrasound assessments of follicular size. These results suggested that ultrasonic monitoring provides a reliable measure of follicular growth and prediction of ovulation, and offers a highly sophisticated scientific tool for the study of reproductive endocrinology.

Ovulation induction with human gonadotropins (hMG or pFSH and hCG) was simultaneously monitored with daily serum 17 beta-estradiol measurements and ultrasound in 38 infertile women. They were subgrouped as follows: A, hypogonadotropic hypogonadism (n. 7); B, polycystic ovary syndrome (n. 13); C, non-PCO chronic anovulation (n. 6); D, unexplained infertility (n. 12). The dose of hMG and the duration of therapy were assessed individually depending on the results of the monitoring when serum estradiol concentration was 500-1500 pg/ml and/or ultrasound showed of a follicle of at least 18 mm, hMG was stopped and hCG was administered 36 hours later. Ovulation was obtained in 61 cases and pregnancy occurred in 12 women out of 64 monitored cycles. The highest pregnancy rate was observed in hypogonadotropic hypogonadism; this group also required the greatest total dose of hMG to obtain ovulation. We confirm that women with PCOS are at increased risk with this therapy, since 5 subjects in our series showed signs of ovarian hyperstimulation in spite of the lowest total dose of FSH administered to this group. We conclude that anovulatory states of various origin are associated with different ovarian sensitivity.

In attempt to optimize gonadotropin-releasing hormone (GnRH) treatment of anovulation, we compared the effect of intravenous GnRH administration at three pulse intervals (PI) during 63 cycles in 30 anovulatory patients who had: (1) amenorrhea secondary to anorexia nervosa (group I: 10 patients, 21 cycles); (2) unexplained anovulation with normal to high luteinizing hormone plasma levels (group II: 12 patients, 24 cycles); and (3) polycystic ovarian disease (PCOD) (group III: 8 patients, 18 cycles). Ovulation was achieved more frequently in group I (85%) than in group II (41%) or in group III (50%). In both groups I and II, the frequency of ovulatory responses was not different with the PI used, and 6 of the 17 women treated for infertility conceived; 3 with 90-minute PIs, 2 with 64-minute PIs, and 1 with 128-minute PIs. In women with PCOD, seven of the nine ovulatory responses and three pregnancies were obtained with 128-minute PIs. The overweight women with PCOD did not respond reliably to GnRH at the doses used, i.e., 4 to 15 micrograms per pulse. In all groups, the urinary estrone and estradiol preovulatory peak, duration of luteal phase, progesterone levels, and preovulatory follicle diameter were unrelated to the frequency of GnRH administration.