Luteal Phase Serum Progesterone Research Articles

Knee Laxities Changes with Sex-steroids throughout the Menstrual Cycle Phases in Athlete and Non-athlete Females.

Objective: Our study investigated changes of knee laxities in athletes and non-athletes females and relationship between knee laxity and sex-steroid at menstrual cycle phases. Methods: Forty six healthy females, twenty four athletes and twenty two non-athletes not on hormone contraceptive pills, had no previous knee injuries and with regular menstrual cycles for 3 consecutive months, participated in the study. Medial and lateral knee laxities were determined by varus-valgus tests at follicular, ovulatory and luteal phases. Serum level of relaxin, estrogen, progesterone and testosterone were determined by ELISA and radioimmunoassay. Results: Knee laxities in athletes and non-athletes at 0° and 20° flexion were the highest in luteal phase with non-athletes possess greater laxity than athletes. Positive correlation between progesterone and relaxin levels with knee laxities were observed. Meanwhile, the levels of both hormones were highest in the luteal phase. Conclusion: Increased medial and lateral knee laxities in athletes and non-athletes associated with high serum progesterone and relaxin levels in luteal phase may contribute toward increased risk of non-contact knee injury. However, lower knee laxity in athletes than non-athletes suggest that exercise could be a protective factor.

#129 : The Ratio of Luteal Phase Serum Progesterone and Estradiol Can be Used to Predict Pregnancy in Frozen Embryo Transfer Cycles

Background and Aims: Low serum progesterone (P) levels on day of embryo transfer (ET) and luteal phase have been associated with poorer pregnancy outcome. This study aimed to know if serum estradiol (E2) and P levels during mid and late luteal phase are related with ongoing pregnancy. Method: The serum E2 and P levels from mid luteal phase (5 days after ET) to the day of the [Formula: see text]-hCG check (11 days after ET) in both fresh and frozen embryo transfer (FET) cycles was investigated between January 2019 and December 2021. Eligible patients were reproductive aged women with a normal uterus. Single blastocyst transfer cycles were included. Estradiol valerate (2 mg/bid) was started from day 3 of cycle as hormone replacement and vaginal micronized P (400 mg/bid) was started 5 days before ET in all FET cycles. The 2-degree polynomial fitted data were analysed and logistic linear model and ROC analysis were performed to assess E2 and P4 polynomial coefficients as a predictive test for ongoing pregnancy. Results: A total of 388 patients were included. The overall pregnancy rate was 43.8% and 31.3% for FET and fresh ET, respectively. On day 5 post ET, the serum P levels correlated significantly with ongoing pregnancy and live birth rates, especially in FET cycles. The ROC curve showed that there is a significant day 5 post ET predictive value of serum P4/E2 levels for pregnancy rate, being the AUC (95% CI) = 0.596 (0.539–0.653) for the combination of both fresh and FET cycles; and 0.611 (0.548–0.674) for FET cycles, with best cut-off values of 0.079 and 0.077, respectively. Conclusion: Serum P levels in mid and late luteal phase days are associated with pregnancy outcome both in fresh and frozen ET cycles. Ongoing pregnancies can be predicted using the day 5 post ET serum P4/E2 levels.

P-298 The live birth rate of the endometriosis patient is significantly increased by high luteal phase serum progesterone in HRT-FET cycles - A cohort study

Abstract Study question What is the optimal serum progesterone (P4) cut-off level for endometriosis patients undergoing hormone replacement therapy frozen embryo transfer (HRT-FET) with intensive exogenous progesterone luteal phase support? Summary answer Endometriosis patients with luteal serum P4 levels≥118nmol/l had significantly higher live birth rates (LBR) compared to patients with lower P4 levels. What is known already A low luteal serum P4 level decreases the reproductive outcome of HRT-FET cycles in the “standard” patient, and an optimal cut-off level of 10ng/ml has been suggested. Interestingly, some studies reported a negative impact of too high serum P4 levels during HRT-FET. The pathology of endometriosis is dominated by an endometrial disruption of progesterone and oestrogen signalling pathways. This results in intra-endometrial oestrogen dominance, and leads to progesterone resistance which negatively impacts endometrial receptivity and function. Until now no study explored the optimal serum P4 level in the endometriosis patient undergoing HRT-FET. Study design, size, duration A cohort study including 262 HRT-FET cycles in 179 patients, undergoing transfer of warmed blastocysts, deriving from freeze all cycles from January 2016 to august 2019. Participants/materials, setting, methods Patients were diagnosed with endometriosis either by laparoscopy or by ultrasound in cases with visible endometriomas. Pre-treatment consisted of 42 days of oral contraceptive pill and 5 days' wash-out, followed by 6 mg oral oestrogen daily. Intensive exogenous progesterone supplementation, including vaginal progesterone gel 90mg/12h commenced when the endometrium was ≥7mm. From the 4th day of progesterone patients also received intramuscular progesterone 50mg. Blastocyst transfer was scheduled for the 6th day of progesterone. Main results and the role of chance The mean P4 level was 103.1 ±44.4nmol/l and the overall positive HCG, live birth (LBR) and total pregnancy loss rates (TPLR) were 60%, 39% and 34%, respectively. The optimal serum P4 cut-off level was 118nmol/l defined as the maximum of the Youden index. No significant differences were seen between patients above or below 118nmol/l as regards age, BMI, fertilisation method or blastocyst score. In a total of 33% of cycles (86/262) the P4 level was ≥118nmol/l, and the unadjusted LBR was significantly higher in the high P4 group 51% (44/86) versus 34% (59/176) (p = 0.006) in the low P4 group. Furthermore, a non-significant difference in TPLR was found: 41% vs 25 % in favour of high P4 (p = 0.066). A logistic regression analysis showed that patients with P4 levels ≥118nmol/l were more likely to achieve a live birth compared to patients with P4 levels <118nmol/l; (odds ratio 2.1 [95% confidence interval 1.2 - 3.7] after adjusting for age, BMI, blastocyst score, blastocyst age (day 5 or day 6) and number of blastocysts transferred. Limitations, reasons for caution Cohort study with data prospectively registered and retrospectively analyzed. The estimated serum cut-off for P4 of 118nmol/l is valid for vaginal progesterone gel 90mg/12h and intramuscular progesterone 50mg from the 4th progesterone day; whether the cut-off is applicable for other progesterone regimens needs to be explored. Wider implications of the findings The optimal luteal P4 level of the endometriosis patient undergoing HRT-FET is significantly higher than that estimated for the "standard" patient due to endometrial progesterone resistance. Luteal phase P4 monitoring is mandatory to obtain the highest LBR in the endometriosis patient undergoing HRT-FET. Trial registration number 1-10-72-4-17

O-242 A randomized controlled trial exploring the effect of different timings of luteal hCG support on luteal phase serum progesterone levels in GnRHa triggered IVF cycles

Abstract Study question Will sequential luteal phase hCG support in GnRHa triggered IVF cycles result in a more optimal progesterone profile compared to single dose luteal hCG dosing? Summary answer Sequential hCG support after GnRHa trigger provides the most optimal progesterone (P4) level during the luteal phase. What is known already The luteal progesterone level at peri- implantation and during the late luteal phase is pivotal to establish and maintain pregnancy. In OHSS risk patients, co-treated with a GnRH antagonist (GnRHant), final oocyte maturation is commonly triggered with a GnRHa, followed by a “freeze all” policy to avoid OHSS. However, in non OHSS risk patients, fresh embryo transfer can still be performed after GnRHa trigger with excellent reproductive outcomes, provided that an optimized luteal phase support (LPS) is used. Study design, size, duration A randomized controlled 3-arm study with 96 enrolled patients from January 2015 until September 2019, at the Fertility Clinic at Odense University Hospital, Denmark. Participants/materials, setting, methods IVF patients in GnRHant co-treatment, with 12-25 follicles ≥12 mm, were randomized into: Group 1: 6500 IU hCG for trigger. Group 2: 0.5 mg GnRHa for trigger followed by 1500 IU hCG on OPU. Group 3: 0.5 mg GnRHa for trigger followed by 1000 IU hCG on OPU and 500 IU hCG on OPU+5. All patients received similar vaginal progesterone as LSP. Eight blood-samples were drawn and analyzed for progesterone during the luteal phase. Main results and the role of chance In total, 69 patients completed the study. The final groups included 25, 22, and 22 patients, respectively. Baseline data were similar between the groups and were comparable in number of retrieved, fertilized, and cleaved oocytes. P4 peaked on OPU+4 in groups 1 (6500 IU hCG) and 2 (GnRHa+ 1500 IU hCG), whereas in group 3 (GnRHa+1000 IU hCG +500 IU hCG) P4 showed a stady increase with a peak on OPU+6. On OPU+6, the P4 level in group 2 (GnRHa+1500 IU HCG) was significantly lower (p = 0.03) compared to the other groups. Further, on OPU+8, the P4 level in Group 3 (GnRHa+1000 IU hCG+500 IU hCG) was significantly higher compared to the other groups (p < 0.001). The area under the curve of P4 were significantly higher in group 3 (GnRHa+1000 IU hCG +500 IU hCG) from OPU+6 until OPU+14, compared individually to each of the other groups. Furthermore, significant inverse association between BMI and P4 level was observed (p = 0.038). Limitations, reasons for caution This study was powered for P4 values, and not the reproductive outcome. The result is restricted to normal/high responder patients, and limits the generalization of the results. Further, the study was un-blinded. Wider implications of the findings Dividing the 1.500 IU hCG for additional support in GnRHa triggered cycles into two administrations of 1000 and 500 IU on day OPU and OPU+5 improves P4 output and is likely to augment pregnancy rates. Trial registration number EudraCT 2013-003304-39

Elinzanetant (NT-814), a Neurokinin 1,3 Receptor Antagonist, Reduces Estradiol and Progesterone in Healthy Women.

ContextThe ideal therapy for endometriosis (EM) and uterine fibroids (UFs) would suppress estrogenic drive to the endometrium and myometrium, while minimizing vasomotor symptoms and bone loss associated with current treatments. An integrated neurokinin-kisspeptin system involving substance P and neurokinin B acting at the neurokinin (NK) receptors 1 and 3, respectively, modulates reproductive hormone secretion and represents a therapeutic target.ObjectiveThis work aimed to assess the effects of the novel NK1,3 antagonist elinzanetant on reproductive hormone levels in healthy women.MethodsA randomized, single-blinded, placebo-controlled study was conducted in 33 women who attended for 2 consecutive menstrual cycles. In each cycle blood samples were taken on days 3 or 4, 9 or 10, 15 or 16, and 21 or 22 to measure serum reproductive hormones. In cycle 2, women were randomly assigned to receive once-daily oral elinzanetant 40, 80, 120 mg, or placebo (N = 8 or 9 per group).ResultsElinzanetant dose-dependently lowered serum luteinizing hormone, estradiol (120 mg median change across cycle: –141.4 pmol/L, P = .038), and luteal-phase progesterone (120 mg change from baseline on day 21 or 22: –19.400 nmol/L, P = .046). Elinzanetant 120 mg prolonged the cycle length by median of 7.0 days (P = .023). Elinzanetant reduced the proportion of women with a luteal-phase serum progesterone concentration greater than 30 nmol/L (a concentration consistent with ovulation) in a dose-related manner in cycle 2 (P = .002). Treatment did not produce vasomotor symptoms.ConclusionNK1,3 receptor antagonism with elinzanetant dose-dependently suppressed the reproductive axis in healthy women, with the 120-mg dose lowering estradiol to potentially ideal levels for UFs and EM. As such, elinzanetant may represent a novel therapy to manipulate reproductive hormone levels in women with hormone-driven disorders.

Daily luteal serum and urinary hormone profiles in the menopause transition: Study of Women's Health Across the Nation.

To further characterize the endocrinology of the menopause transition, we sought to determine: whether relationships between urine and serum hormones are maintained as women enter their sixth decade; whether a single luteal phase serum progesterone (P) is reflective of integrated-luteal urinary pregnanediol glucuronide (uPdg); and whether serum P, like luteal uPdg, declines as women approach their final menses (FMP). The Study of Women's Health Across the Nation (SWAN) Daily Hormone Study's (DHS) is a community-based observational study. A subset of participants underwent a timed, luteal blood draw planned for cycle days 16 to 24 during the same month of DHS collection. Serum-luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol and P, and urine LH, FSH, estrone conjugates (E1c), and daily and integrated luteal uPdg were measured in 268 samples from 170 women. Serum/urine hormone associations were determined using Pearson's correlation and linear regression, adjusted for concurrent age, body mass index, smoking status, and race/ethnicity. Pearson's r ranged from 0.573 (for LH) to 0.843 (for FSH) for serum/urine correlations. Integrated luteal uPdg weakly correlated with serum P (Pearson's r = 0.26, P = 0.004) and explained 7% of the variability in serum P in adjusted linear regression (total R 0.09, P = 0.002). Serum P demonstrated a marginally significant decline with approaching FMP in adjusted analysis (P = 0.04). Urine and serum hormones maintain a close relationship in women into their sixth decade of life. Serum luteal P was weakly reflective of luteal Pdg excretion.

The Role of Oocyte Quality in Explaining "Unexplained" Infertility.

Infertility is described as unexplained when pregnancy does not occur despite ovulation, patent Fallopian tubes, and normal semen parameters. Oocyte developmental competence (or quality) is rate-limiting for pregnancy success as oocytes provide virtually all the cellular building blocks including mitochondria required during embryogenesis. However, available tests estimate oocyte numbers (anti-Müllerian hormone, follicle-stimulating hormone and antral follicle count) and ovulation (luteal phase serum progesterone) but not the third, and most pivotal, oocyte-specific parameter, quality. Severe depletion of the follicular reserve manifests as premature ovarian insufficiency and is an obvious cause of anovulation with overt symptoms and clear diagnostic criteria. In contrast, there are no biomarkers of poor oocyte quality other than through in vitro fertilization when readouts of oocyte quality such as preimplantation embryo development can be assessed. The most common cause of poor oocyte quality is natural aging, which is strongly tied to reduced oocyte mitochondrial efficiency and increased oxidative stress. In younger women, quality may also be impaired due to accelerated aging or sporadic genetic mutations which cause severe defects during oocyte and embryo development. Thus, poor oocyte quality often provides an explanation for infertility, but because it cannot be measured using conventional tests, many cases of infertility are often incorrectly labeled "unexplained." Since female age remains the best predictor of oocyte quality, age over 37 years should be considered an independent diagnostic criterion.

GnRH agonist treatment of luteal phase deficiency in HCG-triggered IVF cycles: a matched case-control study.

This study aimed to identify women with IVF failure associated with low serum progesterone levels after embryo transfer in HCG-triggered cycles and to evaluate the effects of gonadotrophin-releasing hormone (GnRH) agonist, administered after embryo transfer, on serum progesterone and pregnancy outcomes in these cases. Fifty women who failed to achieve an ongoing clinical pregnancy and had abnormally low luteal-phase serum progesterone concentrations in their first IVF attempt were assigned to two matched groups in their subsequent attempt. Twenty-five women were treated with the original protocol plus14 daily injections of GnRH agonist, beginning on the day of oocyte recovery, in their second IVF attempt (group 1). These women were matched to 25 women with the same characteristics and outcomes in their first IVF attempt who underwent the second IVF attempt without the use of GnRH agonist after embryo transfer (group 2). In both groups, the two sequential attempts were compared for serum progesterone concentration 14 days after oocyte recovery and pregnancy outcome. The patients in group 1 had significantly higher progesterone levels 14 days after oocyte recovery in the second attempt compared with the first attempt (P < 0.001), and 12 (48%) of them achieved clinical pregnancy and birth. No significant differences in pregnancy outcome or in the serum progesterone concentration were observed between the first and the second attempt in group 2. In patients with luteal phase deficiency, the administration of GnRH agonist after embryo transfer increases serum progesterone concentration and improves the chance of pregnancy and birth.

Menstrual Patterns in the First Gynecological Year: A Systematic Review.

Understanding what constitutes a normal menstrual cycle during the first gynecological year (GY1) is a common concern of adolescents and clinicians. However, limited high-quality evidence exists. We aimed to summarize published literature regarding menstrual and ovulatory patterns in GY1. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Electronic databases (MEDLINE, Pre-MEDLINE, Embase, Web of Science, CINAHL, Cochrane Library) were systematically searched from database inception to 2018. Eligible studies described menstrual cycles, symptoms, or validated ovulatory data in healthy adolescents in GY1. Two authors independently screened studies, extracted data, and assessed methodological quality. Twenty-two studies involving more than 2000 adolescents were included. Thirteen recorded menstrual cycle and/or symptom data and 14 measured ovulation. Mean cycle length ranged from 32 to 61days and decreased throughout GY1. Mean menses length was 4.9 to 5.4days. Frequent menstrual bleeding was reported in up to 23% of participants, infrequent menstrual bleeding in up to one-third, and "irregular menstrual bleeding" in up to 43%. Dysmenorrhea was reported by 30%-89% of participants. Prevalence of ovulatory cycles identified using luteal phase serum or salivary progesterone or urinary pregnanediol was 0 to 45% and increased throughout GY1. However, all used definitions that would be considered subovulatory in clinical practice. Menstrual and ovulatory patterns in GY1 are diverse and differ from those of adults. A transitional phase of menstrual and ovulatory immaturity is common. However, ovulation, irregular cycles, and dysmenorrhea are not uncommon. As such, safe sexual practice should be advocated and prompt medical management should be accessible.

EFFECTS OF OXYTOCIN AND HUMAN CHORIONIC GONADOTROPIN ON OVULATION IN PATIENTS WITH CLOMIPHENE CITRATE-RESISTANT PCOS

Introduction and Objective: Polycystic ovary syndrome (PCOS) is one of the causes of infertility due to the lack of chronic ovulation. Meanwhile, administration of human chorionic gonadotrophin (HCG) and possibility oxytocin is a method of trigger of ovulation. The present study aimed to investigate theeffect of oxytocin and HCG on ovulation in patients with clomiphene citrate-resistant PCOS. Materials and Methods: This is a double-blind clinical trial performed on 126 patients with clomiphene citrate-resistant PCOS, in Shahid Akbar-Abadi Hospital in Tehran. Ovulation stimulation was performed with (Letrozol 5mg + 10 units of oxytocin),(5,000 units of HCG +Letrozol 5 mg), and(HCG plus oxytocin+5 mg Letrozol). Then information including personal characteristics, contact number, clinic file number, gravidity, parity, history of abortion and previous illness, history of specific drug use, follicle count, dominant follicle size, ovulation symptoms in ultrasound, serum progesterone in luteal phase, and pregnancy outcome were evaluated and recorded in each of the three groups and the results were compared. Findings: Overall, 20% of patients responded to the treatments without any side effect and became pregnant. There was no significant difference in pregnancy rate of infertile women in different groups. In addition, the dominant follicle size and folliclecount in infertile women were studied, and there was no significant difference between the groups ( p -values 0.8 and 0.59, respectively). Of the 91 non-pregnant patients, ovulation induction occurred in 36 women (39.5%) in the next cycles of whom 8 (22.2%) were in the oxytocin group, 10 (27.8%) in the HCG group, and 18 (50.0%) in the oxytocin plus HCG group. Of these 36 patients, 10 (27.8%) were re-induced for ovulation in subsequent cycles of whom 2 (20.0%) were in the oxytocin group, 5 (50.0%) in the HCG group, and 3 (30.0%) in the oxytocin plus HCG group. There was no significant difference in mean endometrial thickness of infertile women treated in different groups ( p =0.1).Comparison of patients in terms of abortion rate showed that among 24 pregnant women, 21 (87.5%) had no abortion and 3 (12.5%) had. Of the 3 cases of abortion, 1 was in the oxytocin group and 2 werein the HCG group. In addition, comparing patients in terms of multiplepregnancy showed 2 cases of twin pregnancy, of which 1 occurred spontaneously 6 months after treatment in the oxytocin plus HCG group,and the second case was in the oxytocin group. In total, 1 out of 24 pregnancies (4.2%) were twin. Finally, there was no statistically significant difference between the three groups in terms of the mean serum progesterone ( p =0.2). Conclusion: Since there was no difference in the fertility rate in threegroups ((Letrozol 5mg + 10 units of oxytocin), (5,000 units of HCG +Letrozol 5 mg), and (HCG plus oxytocin+5 mg Letrozol) and given the low size of the study population, and considering the cost-effectiveness and the fewerside effects of oxytocin, this method(Use of oxytocin(seems effective for trigger of ovulation in clomiphene citrate-resistant PCOS patients.

RETRACTED: Adding l-carnitine to clomiphene resistant PCOS women improves the quality of ovulation and the pregnancy rate. A randomized clinical trial

To evaluate the effectiveness of L-carnitine on improving the ovulation and pregnancy rates as well as adverse metabolic indices in clomiphene-resistant PCOS. Single center, double blinded, superiority, randomized controlled clinical trial. Women's Health Hospital, Assiut University. One hundred and seventy women diagnosed with PCOS were found to be clomiphene resistant. The women were randomly allocated into two groups: Group A (n=85), where patients received 250 mg clomiphene citrate from day three until day seven of the cycle plus L-carnitine (LC) 3g daily; and Group B (n=85) received 250 mg clomiphene citrate with placebo. Primary outcome is cumulative clinical pregnancy rate. Secondary outcomes are changes in serum glucose level and lipid profile. The combination of L-carnitine and CC significantly improve both the ovulation and the cumulative pregnancy rates in clomiphene resistant PCOS (55 (64.4%) vs. 15 (17.4%) and 44 (51.5) % vs. 5 (5.8) %). The number of stimulated follicles reaching ≥17 mm diameter was significantly more in Group A to Group B (2.2 ± 0.77 vs. 0.16 ± 0.79; p<0.0001). Group A needed significantly fewer days for adequate follicular maturation, had a thicker endometrium and higher oestradiol concentration at the time of human chorionic gonadotrophin injection (10.1 ± 0.1mm vs. 6.8 ± 0.4mm; p<0.0001). The same group had a higher mean luteal-phase serum progesterone compared with the control group (13.55 ± 0.99 vs. 10.6 ± 0.98 ng; p<0.0001). A significant difference was found regarding the clinical pregnancy rates (42 (49.4%) vs. (1) 1.1% respectively p value <0.0001). Adding L-carnitine when treating clomiphene-resistant PCOS patients not only improved the quality of ovulation and the pregnancy rate with an acceptable patient tolerability, but also enhanced the patient lipid profile and body mass index.

Evaluation of reproductive function in women treated for bipolar disorder compared to healthy controls

The purpose of the present study was to investigate the reproductive function of women with bipolar disorder (BD) compared to healthy controls. Women diagnosed with BD and healthy controls with no psychiatric history, aged 18-45 years, were recruited from a university clinic and surrounding community. Participants completed a baseline reproductive health questionnaire, serum hormone assessment, and ovulation tracking for three consecutive cycles using urine luteinizing hormone (LH)-detecting strips with a confirmatory luteal-phase serum progesterone. Women with BD (n = 103) did not differ from controls (n = 36) in demographics, rates of menstrual abnormalities (MAs), or number of ovulation-positive cycles. Of the women with BD, 17% reported a current MA and 39% reported a past MA. Dehydroepiandrosterone sulfate and 17-hydroxyprogesterone levels were higher in controls (p = 0.052 and 0.004, respectively), but there were no other differences in biochemical levels. Medication type, dose, or duration was not associated with MA or biochemical markers, although those currently taking an atypical antipsychotic agent indicated a greater rate of current or past MA (80% versus 55%, p = 0.013). In women with BD, 22% reported a period of amenorrhea associated with exercising or stress, versus 8% of controls (p = 0.064). Self-reported rates of bulimia and anorexia nervosa were 10% and 5%, respectively. Rates of MA and biochemical levels did not significantly differ between women with BD and controls. Current atypical antipsychotic agent use was associated with a higher rate of current or past MA and should be further investigated. The incidence of stress-induced amenorrhea should be further investigated in this population, as should the comorbid incidence of eating disorders.

Luteal phase serum progesterone level: a potential predictive marker for pregnancy rate in intracytoplasmic sperm injection.

Background: It is evident that there is a lack of clear consensus on the role of luteal phase serum Progesterone (P) level in the prediction of early pregnancy after controlled ovarian hyperstimulation (COH) protocols in assisted reproductive techniques (ART).Objective: We conducted this study in order to investigate the potential value of luteal phase serum progesterone measurement, in women undergoing ICSI treatment cycles and receiving progesterone supplements, in relation to pregnancy rate.Patients: A total of 68 women aged 20-40 years undergoing their first intracytoplasmic sperm injection (ICSI) cycles in fertility and I.V.F center of Kamal Al samrai hospital.Methods: women consecutively treated by ICSI had Estimation of luteal phase serum Progesterone levels on days 0 and 14 of embryo transfer (ET).Results: 10 pregnancies were achieved (14.7%). Age, basal FSH level, peak E2 level, number of oocytes retrieved, and number of embryos transferred were comparable between pregnant and nonpregnant women. Day-0 and day-14 luteal phase serum Progesterone levels were significantly different between the two groups.Conclusion: Luteal phase serum Progesterone concentration seems to be a promising marker for prediction of early pregnancy in intracytoplasmic sperm injection.

Supplementation of clomiphene citrate cycles with Cimicifuga racemosa or ethinyl oestradiol – a randomized trial

The anti-oestrogenic activity of clomiphene citrate (CC) on the cervical mucous and endometrium may be the reason for the relatively low pregnancy rates in CC induction cycles. Various follicular-phase supplements have been tried to improve cycle outcome in these patients. This study compared follicular-phase supplementation with either phytoestrogen (PE) or ethinyl oestradiol (EE) in CC induction cycles for the treatment of unexplained infertility. A total of 134 patients were randomly allocated to each treatment group (67 each). The PE group needed significantly fewer days for adequate follicular maturation, had a thicker endometrium and higher oestradiol concentration at the time of human chorionic gonadotrophin injection (all P < 0.001). The PE group had higher luteal-phase serum progesterone compared with the EE group. No significant difference was found regarding clinical pregnancy rates (14.0% versus 21.1%, respectively). In conclusion, the cycle characteristics in unexplained infertility women treated with clomiphene citrate induction and timed intercourse improved after follicular-phase supplementation with PE compared with EE supplementation. Further studies are needed to confirm the mechanism beyond these effects.

Occurrence of menstrual cycle related seizure patterns among epileptic women attending the tertiary neurology clinics of the National Hospital of Sri Lanka

Female sex hormones estrogen and progesterone have effects on seizure activity. Patterns of seizure exacerbations associated with the menstrual cycle have been described as catamenial epilepsy. This study was done to investigate the menstrual cycle related seizure occurrence among female epileptics using seizure-menstrual calendars and sex hormonal assays. Frequency and the patterns of seizure occurrence within the menstrual cycles were determined analyzing seizure-menstrual calendars. Luteal phase serum estradiol and progesterone were determined in those with menstrual cycle related seizure patterns to be compared with that of healthy women. Out of 349 epileptics, 6% showed occurrence of perimenstrual, periovulatory or perimenstrual+periovulatory seizure patterns on analysis of seizure-menstrual calendars. These women showed significantly higher luteal serum estradiol concentrations in comparison to age-matched healthy volunteers. There was no significant difference in the luteal serum progesterone concentrations. This study showed menstrual cycle related patterns of seizure occurrence in a minority of Sri Lankan epileptic women, similar to catamenial epilepsy patterns described by previous studies. These seizure patterns may be due to altered hypothalamo-pituitary-gonadal axis function playing a role in the pathophysiology of epilepsy. We suggest the importance of maintaining seizure-menstrual calendars and hormonal studies in all epileptic women to establish the role of hypothalamo-pituitary-gonadal axis in epilepsy and to achieve efficient control of epilepsy in women of childbearing age.

Clinical findings and chlamydia antibody titre as predictors of tubal factor infertility

Objective:To compare the predictive capacity of clinical scoring system and chlamydia antibody titre in predicting tubal disease.Methods:This study included 70 infertile women with normal ovarian and male factors. All women had detailed history taking, general examination, local examination, and vaginal and cervical swabs for culture and sensitivity. A clinical scoring system based on the following variables was used for prediction of tubal disease; age, infertility duration, previous abortion, previous delivery, dysmenorrhea, dyspareunia, evidence of bacterial vaginosis, and tender adnexa. IgG chlamydia antibody titre (CAT) and mid luteal phase serum progesterone were assessed using enzyme immunoassay (ELISA) technique. Tubal abnormality was assessed by hysterosalpingography (HSG) in the follicular phase. The clinical scoring and the CAT were compared by calculating the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio (+LR), negative likelihood ratio (-LR), the relative risk (RR), and the area under the curve (AUC) of the receiver operator curve.Results:CAT was positive in 20 patients (28.57%) out of the 70 studied women. Evidence of tubal disease identified by HSG was present in 34 patients (48.6%). Seropositive women had significantly higher incidence of tubal abnormality compared to seronegative women (p=0.0001). The CAT was significantly higher in women with tubal disease (11.63 ± 7.27) compared to women with normal tubes (6.76 ± 4.02) (z=3.126, p=0.002). The CAT achieved a low sensitivity of 50% and a high specificity of 91.67%. In comparison, the clinical scoring system achieved a balanced sensitivity and specificity of 82.35% and 86.11% respectively. The AUC of the clinical scoring system (0.891) was found to be significantly higher than that of the CAT (0.717).Conclusion:The clinical scoring system proved to be more accurate than the CAT in predicting tubal disease.

Effect of ormeloxifene, a selective estrogen receptor modulator, on biomarkers of endometrial receptivity and pinopode development and its relation to fertility and infertility in Indian subjects

To compare expression of endometrial estrogen (ER) and progesterone (PR) receptors, beta(3)-integrin subunit, leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and pinopodes in Indian women using ormeloxifene as a contraceptive with fertile and infertile subjects during the window of implantation. Controlled, prospective, clinical study. Hospital-based reproductive health unit and research laboratories. Thirteen fertile women, 6 using ormeloxifene (30 mg/week), 29 with primary and 10 with secondary infertility. Transvaginal ultrasonography, midluteal endometrial biopsies, and blood samples. Histologic dating, endometrial thickness, immunohistochemical localization of ER, PR, beta(3)-integrin subunit, LIF, and IL-6 and scanning electron microscopy. Ormeloxifene significantly reduced endometrial thickness, pinopode density, and caused histologic delay with increased epithelial ER and PR and unaltered epithelial beta(3)-integrin subunit expression. Appearance of fully developed pinopodes, down-regulation of epithelial PR, and increased epithelial beta(3)-integrin subunit expression was observed in in-phase endometrium from fertile and infertile women. LIF and IL-6 expression and serum estradiol and progesterone levels remained unaltered between groups. Ormeloxifene-induced effects might produce asynchrony between endometrial and embryo development resulting in implantation failure. Based on unaltered luteal phase serum progesterone concentration, ormeloxifene did not appear to prevent ovulation in any participant.

Depressive behavior and coronary artery atherogenesis in adult female cynomolgus monkeys.

To examine depressive behavior and early coronary artery atherogenesis in 36 socially housed female cynomolgus monkeys, an established model of atherogenesis and depression. Coronary heart disease (CHD) is caused by coronary artery atherosclerosis (CAA) and its sequelae which develop over a period of decades. Thus, in prospective studies of depression and CHD, CAA was likely present at baseline in most subjects who experienced cardiac events. Little is known about the relationship between depression and CAA. The monkeys were free of atherosclerosis before being fed a diet containing moderate amounts of fat and cholesterol for 52 months. Depressed behavior and activity levels recorded in weekly 15-minute focal samples, telemetered 24-hour heart rate, plasma total (TPC) and high-density lipoprotein cholesterol (HDLC), luteal phase serum progesterone concentrations, basal cortisol, cortisol response to corticotrophin-releasing hormone (CRH), and CAA extent were assessed. Time spent in depressed behavior over 4 years was significantly associated with early CAA (r = .73, p < .001), as were activity level, 24-hour heart rate, TPC, HDLC, cortisol response to CRH, and mean peak progesterone (all p < or = 0.05). Depressed females had four times the CAA compared with nondepressed females. Depression in primates is associated with perturbations in multiple CHD risk factors and accelerated early atherogenesis. These data are consistent with the hypotheses that depression and CAA both stem from a common mechanism and that depression may cause CAA.

Endocrine Features of Menstrual Cycles in Middle and Late Reproductive Age and the Menopausal Transition Classified According to the Staging of Reproductive Aging Workshop (STRAW) Staging System

Female reproductive aging based on changes in menstrual cycle length and frequency progresses through a number of stages as defined by the Stages of Reproductive Aging Workshop (STRAW) staging criteria. This paper provides a comprehensive description of the endocrine features associated with the STRAW stages. Healthy women aged 21-35 and 45-55 yr submitted three blood samples a week over a single menstrual cycle. They were classified as mid-reproductive age (n = 21), late-reproductive age (n = 16), early menopause transition (n = 16), and late menopause transition (n = 23). There were nine, one, zero, and two anovulatory cycles identified in the late menopause transition, early menopause transition, late-reproductive age, and mid-reproductive age groups, respectively. Ovulatory cycle FSH, LH, and estradiol levels increased with progression of STRAW stage (P = 0.001, P < 0.01, and P < 0.05, respectively), and mean luteal phase serum progesterone decreased (P < 0.01). Early cycle (ovulatory and anovulatory) inhibin B decreased steadily across the STRAW stages (P < 0.01) and was largely undetectable during elongated ovulatory and anovulatory cycles in the menopause transition. Anti-Mullerian hormone decreased markedly (10- to 15-fold) and progressively across the STRAW stages (P < 0.01 and P < 0.001, respectively). Progression through the STRAW stages is associated with elevations in serum FSH, LH, and estradiol and decreases in luteal phase progesterone. The marked fall in inhibin B and particularly anti-Mullerian hormone indicate that they may be useful in predicting STRAW stage but future analyses of early cycle measurements on larger cohorts are needed to draw predictive conclusions.

Bleeding patterns in women using intramuscular progesterone for luteal support in in-vitro fertilisation cycles

This paper aims to evaluate the effects of i.m. progesterone on bleeding patterns after in-vitro fertilisation embryo transfer (IVF-ET). It is a retrospective cohort study conducted in the reproductive endocrinology and IVF department of a teaching hospital. One hundred consecutive women were studied who had undergone IVF-ET using 'long protocol' stimulation with leuprolide acetate-recombinant follicle stimulating hormone (rFSH) and who did not become pregnant. Intramuscular (i.m.) progesterone (50 mg once daily) was started the day before oocyte retrieval and continued for a minimum of 12-14 days following embryo transfer. The main outcome measures were time interval between oocyte retrieval and onset of bleeding, luteal phase serum progesterone and oestradiol (E2) levels, and midluteal endometrial thickness. Of the 100 patients whose charts were reviewed, 67 bled (group A) before progesterone treatment was discontinued (17 days after oocyte retrieval) and 33 (group B) bled after progesterone treatment was discontinued (&gt; 17 days). Mean onset of bleeding was 16.2 ± 2.6 days after oocyte retrieval. Serum progesterone concentrations were similar in the two groups on the day of hCG administration, whereas progesterone concentrations (in-group B) were higher on days 7 and 15 after oocyte retrieval. No statistically significant differences were found between two groups with respect to mean midluteal endometrial thickness and mean serum E2 concentrations on days 0, 7 and 15. The results suggest that i.m progesterone administration for luteal support in assisted reproduction cycles elongates luteal phase in some patients due to supraphysiological serum progesterone levels. However, most patients start to bleed in the absence of pregnancy despite continued progesterone treatment.