Mid-luteal Serum Progesterone Levels Research Articles

Exogenous progesterone rescue in patients with low mid-luteal serum progesterone levels undergoing true natural vitrified-warmed blastocyst transfer.

To explore whether a 25mg subcutaneous progesterone daily rescue daily improves the reproductive outcomes in patients with low serum progesterone (P4) levels (7-10ng/mL), measured one day before true natural cycle (t-NC) frozen embryo transfer (FET). A cohort study of 192 women undergoing t-NC warmed blastocyst transfer. Patients were stratified into three different groups based on serum P4 levels on the FET-1day: patients who had serum P4 levels of 7-10ng/mL and underwent rescue progesterone administration (rescue group), patients with serum P4 levels of 7-10ng/mL without progesterone administration (non-rescue group), and patients with serum P4 > 10ng/mL on FET-1day (control group). The primary outcome was possible differences in live birth rate (LBR) between groups. The LBRs for the serum P4 7-10ng/mL without rescue, 7-10ng/mL with rescue, and > 10ng/mL (control) groups were 41%, 46%, and 52%, respectively (p = 0.61). The estimated adjusted probability of live birth for serum P4 7-10ng/mL without rescue, 7-10ng/mL with rescue, and > 10ng/mL (control) groups were also comparable: 43.5% (95% CI, 20.0-70.4%), 49.8% (95% CI, 28.1-71.6%), and 57.4% (95% CI, 44.0-69.8%), respectively. Serum P4 levels higher than 7ng/mL seem to secure LBRs in patients undergoing t-NC FET. A rescue policy consisting of a daily subcutaneous 25mg progesterone dose in patients with serum P4 levels 7-10ng/mL does not further enhance LBRs when compared to those patients with similar serum P4 levels without rescue.

Midluteal serum estradiol levels are associated with live birth rates in hormone replacement therapy frozen embryo transfer cycles: a cohort study

ObjectiveTo study whether mid-luteal serum estradiol (E2) levels are associated with the Live Birth Rate in Hormone Replacement Therapy FET cycles in patients with optimal mid-luteal serum progesterone (P4) levels. DesignObservational prospective cohort study of 412 women having a Hormone Replacement Therapy FET single blastocyst transfer from January 2020 to November 2022. SubjectsThe Hormone Replacement Therapy FET priming regimen included oral estradiol (6mg/24h) administered in the evening, followed by vaginal progesterone (400mg/12h). Serum E2 and P4 levels were measured in a standardized manner, 2-4 hours after the latest progesterone administration and 9-14 hours after estradiol administration on the day of blastocyst transfer, day 6 of progesterone administration. Patients with serum P4 <11ng/mL (35nmol/l) on the day of transfer received additional rectal progesterone (400mg/12h). No additional estradiol was administered. Main Outcome MeasuresThe primary outcome was Live Birth Rate in relation to E2 levels at blastocyst transfer day. ResultsThe optimal serum E2 range correlating with ongoing pregnancy was ≥292pg/ml <409pg/ml (≥1070pmol/l and <1500pmol/l). The Live Birth Rate was 59% (60/102) if E2 levels were within this range, whereas a significantly lower Live Birth Rate of 39% (101/260, p=0.001) was seen in patients if E2 levels were <292pg/ml (<1070pmol/l), and of 28% (14/50, p<0.001) if E2 levels were ≥409pg/ml (≥1500pg/mL). In a logistic regression analysis, adjusting for serum progesterone level ≥11ng/mL or <11ng/mL (≥35nmol or <35nmol/l) on the day of transfer, BMI, age at oocyte retrieval, day 5 or 6 vitrified blastocyst and blastocyst score, the adjusted risk difference (RD) of a live birth was -0.21 [-0.32; -0.10] when the E2 level was <292pg/mL (<1070pmol/l) and -0.31 [-0.45; -0.18] if the E2 level was ≥409pg/ml (≥1500pmol/l) compared to E2 levels ≥292pg/ml <409pg/ml (≥1070 <1500pmol/l). Importantly, only 25% of patents had optimal levels. ConclusionThe study shows a significant association between serum E2 levels and reproductive outcomes in a Hormone Replacement Therapy FET cohort in which optimal serum progesterone levels were secured. Mid-luteal serum E2 levels are associated with Live Birth Rate in Hormone Replacement Therapy FET cycles and E2 levels should neither be too high nor too low.

Does mid-luteal progesterone predict pregnancy in intrauterine insemination cycles following sequential clomiphene citrate and gonadotropin treatment?

This study aimed to determine whether serum mid-luteal progesterone (MLP) levels measured in the current treatment cycles of infertile women undergoing controlled ovarian hyperstimulation and intrauterine insemination following the sequential use of clomiphene citrate and gonadotropin may predict pregnancy. A total of 107 consecutive anovulatory women were included in this prospective cohort study. Patients with other causes of infertility were also excluded from the study. None of the patients received progesterone treatment for luteal phase support. The data recorded for each woman included age, body mass index, infertility type and duration, basal hormone levels, and previous and current cycle characteristics with MLP levels. Ovulation was confirmed using MLP and sonographic evaluation in all patients. An MLP level of > 3 ng/mL was regarded as a sign of ovulation. After treatment, the patients were divided into 2 groups according to the presence or absence of pregnancy, and the obtained data were compared between the groups. There were no significant differences in age, body mass index, or basal hormone levels between the 2 groups (all P > .05). However, the duration of infertility was significantly shorter in the pregnancy group (P = .003). The anovulation rate in this cohort was 18.7% (n = 20). A total of 15 (14%) were examined. MLP levels were 25.1 ± 13.8 ng/mL and 18.3 ± 14.5 ng/mL in the pregnant and nonpregnant groups, respectively (P:.089). Based on the receiver operating characteristic curve analysis, it was determined that there was no predictive value of the mid-luteal phase progesterone level for pregnancy in patients in whom ovulation was detected. Mid-luteal serum progesterone levels did not predict pregnancy in infertile women who underwent controlled ovarian hyperstimulation with sequential clomiphene citrate plus gonadotropin treatment and intrauterine insemination.

P-500 Relationship of midluteal serum progesterone levels and pregnancy outcomes after day-3 embryo-transfer(ET) in hormonal replacement therapy (HRT) cycles with intramuscular progesterone: a prospective cohort study

Abstract Study question Does midluteal(day-9 of progesterone) serum progesterone level in HRT cycles with intramuscular progesterone affect the clinical pregnancy rate (CPR)/early miscarriage rate(MR) and live birth rate(LBR)? Summary answer Midluteal serum progesterone between 32.2-43.7ng/ml results in significantly greater CPR versus that with lower/higher levels and significantly greater LBR compared to that with lower levels. What is known already Evidence points to low serum progesterone levels at the time of FET being associated with lower ongoing pregnancy rates. Recently, the relation of midluteal serum progesterone levels in HRT cycles with vaginal progesterone as luteal phase support (LPS) has been elaborated indicating better pregnancy outcomes with an optimum range of serum progesterone/higher levels. There is no data establishing the association of pregnancy outcomes with midluteal serum progesterone levels when intramuscular progesterone is used as LPS in HRT cycles. Study design, size, duration A prospective cohort study conducted between December 2019-March 2022 at a tertiary centre with 196 patients(204 cycles), both-autologus(AO)-56.3% and donor oocytes(DO)- 43.6%: fresh ET-16.6% and frozen ET(FET)-83.3% with similar ICSI, vitrification and ET protocols(2/3 Grade A day-3 embryos). CPR, early MR (≤13 weeks miscarriage/clinical pregnancy) and LBR (≥28 weeks, LBs/ETs) were compared. Serum progesterone was measured on the morning of day-5 post-ET(day 9th from the start of progesterone). Most patients delivered at the same institute. Participants/materials, setting, methods Patients were non-smokers with normal hysteroscopy. Oral estradiol 6-8mg was initiated from Day 1-2 (for 10-17 days). When ET ≥ 7mm and serum progesterone &amp;lt;1ng/ml, intramuscular progesterone 100mg/day was started (daily till day-4 post-ET, then every 3rd day till week 8). Vaginal progesterone gel was added from day 5 post-ET till week 10. Serum progesterone levels were categorized in tertiles. Chi-square, t-tests and multiple regression analysis was used for statistical analysis. Two-tailed P&amp;lt;.05 indicated statistical significance. Main results and the role of chance Mean age was 34.76±5.36 years with a mean BMI 26.4±4.38kg/m2 Overall, CPR was 106/204(51.9%), LBR 78/204(38.2%) and early MR 28/106(26.4%) Midluteal serum progesterone levels ranged from 11.1-261ng/ml and were divided into tertiles(T) T1&amp;lt;32.0ng/ml(n = 68),T2 32.2-43.7ng/ml(n = 68),T3 &amp;gt;43.7ng/ml (n = 68) Median progesterone levels of T1,T2,T3 were 27.7ng/ml(Interquartile range [IQR] 7.0), 38.4ng/ml (IQR 5.0) and 51.2ng/ml (IQR 12.6) respectively. Mean age and mean BMI was not significantly different across the tertiles P=.27, P=.20 respectively CPR was significantly different across T1 32/68(47%),T2 45/68(66.1%)and T3 29/68(42.6%) P=.014. CPR was significantly more in T2 versus T1 and T3, (OR:2.2, 95%CI:1.1-4.4 P =.02) and (OR:2.6,95%CI:1.3-5.3, P=.006), respectively. T3 versus T1, P =.60 LBR was also significantly different across the tertiles [T1 20/68(29.4%), T2 34/68(50%),T3 24/68(35.3%) P=.03] LBR in T2 was significantly more than in T1(OR: 2.4,95% CI:1.2-4.9, P=.02). There was no significant difference betweenT3 versus T1 and T2 versus T3, P=.46, P=.08, respectively. Early MR wasn’t significantly different across T1 12/32(37.5%), T2 11/45(24.4%) and T3 5/29(17.2%), P=.18 Serum progesterone levels were not significantly affected by age r = 0.0257, P=.71 or BMI r = 0.0097, P=.89 Multivariate logistic regression showed that age affected CPR after adjusting for BMI, midluteal serum progesterone levels, origin of oocytes, fresh ET/FET(AOR 0.92: 95% CI:0.86-0.98, P=.01). Limitations, reasons for caution This is a single centre study with limited sample size. Including the measurement of serum progesterone at the time of ET would have given a better perspective of the patient specific behavior of progesterone as LPS. Larger studies with different LPS protocols are needed to validate the results. Wider implications of the findings In HRT cycles with intramuscular progesterone, an optimum midluteal serum progesterone level is related to better pregnancy outcomes. Factors causing the wide variation of progesterone levels need to be evaluated so as to individualize the dose. Identifying the appropriate time frame for optimising the midluteal progesterone levels should be explored. Trial registration number not applicable

Endogenous progesterone in unexplained infertility: a systematic review and meta-analysis

PurposeTo investigate the possibility that altered actions of endogenous progesterone affect receptivity and contribute to unexplained infertility (UI).MethodsTwo authors electronically searched MEDLINE, CINAHL and Embase databases from inception to 6 July 2022 and hand-searched according to Cochrane methodology. We included all published primary research reporting outcomes related to endogenous progesterone in natural cycles in women with UI. Studies were assessed for risk of bias using a modified Newcastle–Ottawa Score or NHLBI Score. We pooled results where appropriate using a random-effects model. Findings were reported as odds ratios or mean differences.ResultsWe included 41 studies (n = 4023). No difference was found between the mid-luteal serum progesterone levels of women with UI compared to fertile controls (MD 0.74, − 0.31–1.79, I2 36%). Women with UI had significantly higher rates of ‘out-of-phase’ endometrium than controls. Nine out of 10 progesterone-mediated markers of endometrial receptivity were significantly reduced in women with UI compared to fertile controls (the remaining 1 had conflicting results). Resistance in pelvic vessels was increased and perfusion of the endometrium and sub-endometrium reduced in UI compared to fertile controls in all included studies. Progesterone receptor expression and progesterone uptake were also reduced in women with unexplained infertility.ConclusionsEnd-organ measures of endogenous progesterone activity are reduced in women with UI compared to fertile controls. This apparently receptor-mediated reduction in response affects endometrial receptivity and is implicated as the cause of the infertility. Further research is required to confirm whether intervention could overcome this issue, offering a new option for treating unexplained infertility.Trial registrationPROSPERO registration: CRD42020141041 06/08/2020.

A drop in serum progesterone from oocyte pick-up +3 days to +5 days in fresh blastocyst transfer, using hCG-trigger and standard luteal support, is associated with lower ongoing pregnancy rates.

A drop in serum progesterone from oocyte pick-up +3 days to +5 days in fresh blastocyst transfer, using hCG-trigger and standard luteal support, is associated with lower ongoing pregnancy rates.

The impact of preovulatory versus midluteal serum progesterone level on live birth rates during fresh embryo transfer.

Conflicting evidence still prevails concerning the effect of preovulatory elevated progesterone (EP4) on reproductive outcomes in fresh embryo transfer (ET). However, few studies have analyzed the effect of EP4 on the likelihood of pregnancy using multivariate regression approach. The potential confounding factors tested in these studies were limited to either patient's characteristics or to stimulation related parameters. Yet, several studies have shown that postovulatory parameters such as midluteal progesterone (P4) level may be considered as a proxy variable of endometrial receptivity as well. The aim of the present study was to estimate the independent effect of preovulatory P4 effect, if any, on the probability of live birth (LB) by considering the midluteal endocrine profile when controlling for the potential confounding factors. This is a secondary data analysis of a cohort of fresh IVF/ICSI cycles triggered with GnRH agonist (n = 328) performed in a single IVF center during the period 2014-2016. Patients contributed only one cycle and were stratified into four groups according to preovulatory P4 quartiles. We assessed the association between preovulatory P4 and the odds of LB calculated by logistic regression analysis after controlling for the most clinically relevant confounders. The primary outcome measure: Live birth rates (LBR). Both preovulatory and midluteal P4 were significantly correlated with the ovarian response. Logistic regression analysis showed that preovulatory serum P4 did not have a significant impact on LBR. In contrast, midluteal serum P4 level was an important independent factor associated with LBR. The optimal chance of LBR was achieved with midluteal serum P4 levels of 41-60 ng/ml, [OR: 2.73 (1.29-5.78); p< 0.008]. The multivariate analysis suggests that the midluteal P4 level seems to impact LBR more than the preovulatory P4 level in women undergoing IVF treatment followed by fresh ET.

Effect of Individualized Progesterone Supplementation for Luteal Support in Frozen-Thawed Cycles on Pregnancy Outcomes

Objective: In frozen-thawed embryo transfer (FET) cycles, preparing a synchronous endometrium for the embryo is essential. Aim of this study is to provide individualized luteal support in hormonally replaced FET cycles, and to evaluate mid-luteal serum progesterone levels and pregnancy outcomes.Study Design: In this prospective cohort study, 30 patients were included in a university hospital in six month-period. Serum progesterone level on embryo transfer day was monitored, and if it was found to be below the lower limits defined by previous studies (10 ng/mL), additional 100 mg intramuscular micronized progesterone was administered once.Mid-luteal progesterone levels and pregnancy outcomes were recorded.Results: There was no significant difference between mid-luteal progesterone levels of the patients whose transfer day progesterone was above and below 10 ng/mL (p=0.481). Although clinical pregnancy rate tended to be higher in patients whose mid-luteal progesterone was above 10 ng/mL, it was also not statistically significant.Conclusion: This is the first study in which vaginal progesterone treatment was supported by intramuscular progesterone according to serum progesterone values for the purpose of individualized progesterone support. Significant difference was not found in pregnancy outcomes. However, further studies are required to optimize management and improve pregnancy rates in hormonally treated FET cycles.

Revisiting the role of serum progesterone as a test of ovulation in eumenorrheic subfertile women: a prospective diagnostic accuracy study

To estimate the prevalence of ovulatory cycles in eumenorrheic subfertile women and compare the diagnostic accuracy of a single ultrasound with serum midluteal progesterone measurement in detecting ovulatory cycles. Prospective diagnostic accuracy study. University-level hospital. A total of 208 subfertile eumenorrheic women. None. To estimate the prevalence of ovulatory cycles in eumenorrheic women and compare the diagnostic accuracy of a single, well-timed ultrasound scan (index test) with serum progesterone measurement (reference test) by calculating the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive likelihood ratio (LR+) and negative likelihood ratio (LR-). The prevalence of ovulatory cycles among subfertile eumenorrheic women was 92.9% and 99.5% when midluteal serum progesterone level and ultrasound scanning were used as the reference test, respectively. The sensitivity, specificity, PPV, and NPV of ultrasound in identifying ovulatory cycles were 100%, 7.1%, 93.4%, and 100%, respectively. The LR+ and LR- were 1.1 and 0, respectively. The agreement between the ultrasound and serum progesterone was almost perfect (prevalence and bias-adjusted kappa = 0.81. The prevalence of ovulatory cycles in eumenorrheic subfertile women appears to be high. A single well-timed ultrasound can be performed to identify ovulatory cycles during the infertility workup in eumenorrheic women.

Impact of Luteal phase clomiphene citrate on endometrial thickness and clinical pregnancy rates in women with polycystic ovary syndrome

Objective: To compare between luteal phase clomiphene citrate and second cycle day clomiphene citrate on the thickness of the endometrium and clinical pregnancy rates in women with polycystic ovary syndrome. Methods: a prospective observational study conducted on 196 women with Polycystic ovary syndrome divided into two groups: Group 1 (98 patients) received 100mg of clomiphene citrate daily for 5 days starting on second cycle day and Group 2 (98 patients) received 100mg of clomiphene citrate daily starting in the luteal phase before onset of withdrawal bleeding for 5 days. Treatment and follow up applied for three cycles. Outcome measures were collected and analyzed and women who got pregnant were followed until 12 weeks of pregnancy. Results: no significant differences between the two groups regarding pre-ovulatory endometrial thickness (8.3mm in group 1vs 8.8mm in group 2), number of mature follicles (1.62 in group 1vs 1.57 in group 2) and mid-luteal serum progesterone levels(14.63ng/ml in group 1vs 14.9ng/ml in group 2). 34 women (35%) got pregnant in group 1 and 37 women (38%) in-group 2 and three patients had miscarriage in each group without any statistical significance. Conclusion: the present study does not support luteal clomiphene citrate over second cycle day clomiphene citrate to induce ovulation in infertile women with polycystic ovary syndrome.

Impact of mid-luteal serum progesterone levels on pregnancy outcome in fresh and frozen embryo transfer cycles in women of Indian ethnicity

Context: Luteal phase defect has been identified in all assisted reproductive technology cycles, necessitating progesterone supplementation. Aims: The aim of our study was to assess whether mid-luteal serum progesterone (P) levels' impact pregnancy outcome in fresh and frozen embryo transfer (FET) cycles. Settings and Design: A total of 145 women undergoing embryo transfer (ET) were prospectively enrolled and received standard luteal phase support. Methodology: Serum progesterone levels were assessed for all the patients in the mid-luteal phase. Patients were divided into groups based on the type of ET performed. Group A – fresh ET and Group B – FET. These groups were further subdivided based on mid-luteal serum P levels being below (Groups A1/B1) or above 15 ng/mL (Groups A2/B2). Progesterone levels were correlated with the clinical pregnancy outcome. Statistical Analysis Used: Chi-square test was used for qualitative analysis, and student's t-test was used for comparison of means. Results: Patients with mid-luteal serum P levels Conclusions: This study suggests that, in Indian women, mid-luteal serum P levels biochemical pregnancies) cycles. Individualizing luteal phase support by measuring serum progesterone levels might help to enhance pregnancy outcomes.

OVARIAN STROMAL BLOOD FLOW AFTER LAPAROSCOPIC OVARIAN DRILLING IN WOMEN WITH POLYCYSTIC OVARY SYNDROME

Women with polycystic ovary syndrome have significant difference in their ovarian stromal blood flow indices when compared to women with normal ovaries. The intra-ovarian blood flow is assessed by studying small arteries in the ovarian stroma not close to the surface of the ovary or near the wall of the follicles. Aim: To assess the value of changes in Doppler indices of ovarian stromal blood flow and hormonal profile in women with PCOS and previously described as being clomiphene citrate resistant in predicting the clinical outcome of laparoscopic ovarian drilling as regard ovulation. Study design: This study is interventional study. Setting: Department of Obstetrics and Gynecology (Ultrasound and Gynecologic endoscopy units), Faculty of Medicine, Zagazig University. Patients' criteria: Women with PCOS according to Rotterdam criteria, 2003, aged 18-35 years. All women in the study were free of any medical illness and had not received any medications in the last 6 months before the study apart from incremental doses of clomiphene citrate with its failure to induce ovulation in them (clomiphene citrate resistant). Hysterosalpingography and husband semen analysis were normal in all subjects. Sample size: 59 PCOS patients. Procedures: After measuring peak systolic blood flow velocity (PSV), pulsatility index (PI) and resistance index (RI) within the ovarian stroma using two dimensional colour Doppler transvaginal sonography and measuring the serum concentrations of FSH, LH and total testosterone of 59 PCOS patients, laparoscopic ovarian drilling was done (4 punctures in each ovary using 40 watts monopolar electrocautery for 4 seconds). Ovulation was evaluated by serial ultrasound and mid luteal serum progesterone level in the first post-operative menstruation. Results: Within 10 weeks of laparoscopic ovarian drilling (LOD), LH decreased significantly from (13.1 + 1.9) before LOD to (6 + 0.6) after LOD and total testosterone decreased significantly from (1.04+0.23) to (0.51 + 0.2). As regard FSH, it increased significantly from (6.16+ 0.34) before LOD to (7.6 + 0.8) after LOD. PSV decreased significantly from (11.9 + 1.8) before LOD to (7.44 + 1.5) after LOD. Also, PI increased significantly from (2.02 + 0.56) before LOD to (2.98 + 0.5) after LOD. As regard RI, it increased significantly from (0.75 + 0.06) before LOD to (0.86 + 0.05) after LOD. There was significant negative correlation between total testosterone and PI (r = 0.49, p. value < 0.01), highly significant negative correlation between total testosterone and RI (r = 0.41, p. value < 0.001) and significant positive correlation between total testosterone and PSV (r = o.32, p. value< 0.05). Conclusion(s): PCOS patients to whom Laparoscopic ovarian drilling was done usually experienced reduction in their blood flow within the ovarian stroma. There was statistically significant correlation between hormonal profile and changes in the blood flow within the ovarian stroma in those patients. This may be valuable in predicting the clinical outcome of LOD as regard ovulation and pregnancy. Key Words: Ovarian stromal blood flow, laparoscopic ovarian drilling, Doppler, polycystic ovary syndrome.

The quality of ovulation is strained in normal women

‘Ovulatory dysfunction’ bears the imprimatur of a succinct medical diagnosis, but what does it really mean and above all, how do you diagnose it, especially in women with a normal menstrual history? Although we have multiple measures in our modern toolbox: ultrasound for daily follicular monitoring, hormonal assays of serum, urine and saliva (some for instance LH available over the counter to our patients), and even, heaven forbid, an endometrial biopsy; these are expensive, invasive and labor intensive for both physician and patient to document, and often lacking in evidence-based cutoffs. The bottom line is that the most common clinical practice to screen for ovulatory dysfunction is a menstrual history. Much of our knowledge of the normal length of the menstrual cycle and the effects of age on the menstrual cycle comes from the classic studies of Treloar et al. (1967) which were based on menstrual diaries collected on the back of a postcard, beginning in young women recruited during their college years and then collected over their lifetimes. We are likely to assume that a woman is ovulating regularly if her menstrual cycle length is 21–35 days (thanks to Treloar). Therefore, the BioCycle study by Hambridge et al. (2013) reported in this issue of the journal offers important and novel data about ovulatory function in normal women, including the frequency of anovulation (12%), and the influence of anovulation upon ovulatory cycles (adversely in terms of integrated serum estrogen and progestin measures). The BioCycle study investigators prospectively enrolled a cohort of 259 healthy, menstruating women, 18 –44 years of age (excluding confounders such as hormonal use, history of ovulatory disorders, etc.). Women were asked to provide eight timed serum specimens during each of two menstrual cycles, and these were timed in relation to self-monitoring for ovulation using urinary LH and estrogen kits, to allow for comparison at similar phases of the cycle. The current study includes 250 women who provided (at least some) data from two menstrual cycles. A significant strength of the study is the retention and compliance in the protocol for such a large number of women. Over 94% of the women completed seven or more of the planned visits per cycle (far exceeding the average dropout in randomized clinical trials!) and all women had at least five visits per cycle. An additional strength is that the investigators studied more than one menstrual cycle in each subject, and carefully collected confounders of the menstrual cycle in the cohort. The investigators used a serum progesterone cut-off point (.5 ng/ml) to categorically determine whether ovulation took place in the cycle, analogous to our own clinical practice of documenting ovulation with a mid-luteal serum progesterone level. Overall 12% of the women with a normal menstrual history had at least one anovulatory cycle and of these 3% had two anovulatory cycles. Women with two ovulatory cycles were older (mean age of this group was 28 years) and women with anovulatory cycles were significantly younger (the mean age of women with one anovulatory cycle was 5 years younger and with two anovulatory cycles 8 years younger). Women with anovulatory cycles were also more likely, not surprisingly, to be unmarried and nulliparous, and anovulation was not associated with smoking, former OCP use or physical activity. However, the most important and novel observation of this study is the effect of anovulation on subsequent ovulation, and hence the title of this editorial. The investigators utilized complex modeling to construct the menstrual cycle (and also created some elegant figures) based on their repeated serum hormonal measures, and divided the subjects categorically on the basis of their ovulatory status. They found diminished integrated levels of serum sex steroids in the ovulatory cycles of women who also had one anovulatory cycle (and this was independent of the temporal relation of the ovulatory cycle to the anovulatory cycle), compared with those women who had two ovulatory cycles. In regard to integrated progesterone levels there was a dose– response stepdown in integrated progesterone levels with highest in the women with two ovulatory cycles, followed by those with one ovulatory/one anovulatory cycle followed by those with two anovulatory cycles. This may be (in the periodic ovulators) the clearest depiction of the long hypothesized luteal phase defect (Jones, 2008) that I have seen. While these hormone levels represent only a surrogate of oocyte quality or endometrial function, and ultimately fecundity, they offer evidence, that documentation of an anovulatory cycle in a women suggests altered and likely diminished ovulatory quality (with potential downstream endometrial effects) in these women when they do ovulate. In other words, the anovulatory

Premenstrual dysphoric disorder in women with epilepsy: Relationships to potential epileptic, antiepileptic drug, and reproductive endocrine factors

The purpose of this prospective observational investigation was to determine whether the frequency of premenstrual dysphoric disorder (PMDD) and the severity of PMDD symptoms differ between women with epilepsy and controls without epilepsy and whether there exists a relationship between the severity of PMDD symptoms and some epileptic, antiepileptic drug, and reproductive endocrine features. The results suggest that epilepsy, antiepileptic drug levels, ovulatory status, and hormone levels and ratios may all influence PMDD in women with epilepsy. PMDD severity scores may be greater in people with right-sided than in those with left-sided epilepsy, and in people with temporal than in those with nontemporal epileptic foci. PMDD severity scores may be greater with anovulatory cycles, and scores may correlate negatively with midluteal serum progesterone levels and positively with midluteal estradiol/progesterone ratios. Mood score may vary with particular antiepileptic drugs, favoring carbamazepine and lamotrigine over levetiracetam. PMDD severity scores may correlate directly with carbamazepine levels, whereas they correlate inversely with lamotrigine levels.

Luteal Support for IVF/ICSI Cycles with Crinone 8% (90 mg) Twice Daily Results in Higher Pregnancy Rates Than with Intramuscular Progesterone

The use of progesterone for luteal support has been demonstrated to be beneficial in assisted reproductive cycles, yet the optimal route of progesterone administration has still not been established. This article is a retrospective study in a tertiary reproductive medical unit to compare luteal progesterone supplementation with vaginal gel or intramuscular progesterone. A total of 144 in vitro fertilization or intracytoplasmic sperm injection cycles were analyzed, 67 cycles using vaginal gel 90 mg twice daily and 77 cycles using intramuscular progesterone 50 mg daily as luteal support. Both groups had similar mean age, cause of infertility, baseline hormone levels, dosage of recombinant follicle-stimulating hormone, number of retrieved and fertilized oocytes, and number of transferred embryos. The vaginal gel group had significantly lower mid-luteal serum progesterone levels but higher implantation rate (32.5% vs. 18.5%, p = 0.001) and ongoing pregnancy rate (55.2% vs. 32.5%, p = 0.006). Within each group, mid-luteal serum progesterone levels between pregnant or non-pregnant patients were comparable. For patients with serum estradiol levels on day of human chorionic gonadotropin greater than 5,000 pg/mL, vaginal gel still resulted in better ongoing pregnancy and implantation rates. The use of vaginal progesterone gel twice daily for luteal support results in better pregnancy outcomes than intramuscular progesterone. A high local progesterone effect from vaginal gel might improve endometrial receptivity under extraordinarily high serum estradiol levels.

Clinical aspects and luteal phase assessment in patients with recurrent vulvovaginal candidiasis

Objective This study was undertaken to characterize the patients with recurrent vulvovaginal candidiasis. Study design Basic data of personal history and history of recurrent vulvovaginal candidiasis, lower genital tract symptoms and signs in 50 patients were analyzed in this longitudinal follow-up study including the determination of midluteal serum progesterone and urinary pregnanediol levels during the luteal phase in 84 cycles (recurrent vulvovaginal candidiasis) and 60 cycles (healthy controls). Results All patients suffered primary idiopathic form of recurrent vulvovaginal candidiasis. Frequently, there was a striking discrepancy between severe symptoms and clinical finding, which was often negligible or normal. There was no redness and no or minimum discharge in 52% of culture documented attacks. In contrast to the healthy controls, the patients had significantly lower levels of progesterone ( p < 0.01) as well as those of urinary pregnanediol ( p < 0.05). Conclusion Culture positive attacks in patients with recurrent vulvovaginal candidiasis represented rather a form of vulvovaginal discomfort than attacks of vulvovaginal candidiasis with typical inflammatory changes. Significantly lower progesterone levels in the RVVC patients as compared to the healthy controls suggest a link between an altered hormonal status and one of possible causes of RVVC in these women.

Donor Oocyte IVF Practice Patterns in North America: Results of a National Survey

Donor Oocyte IVF Practice Patterns in North America: Results of a National Survey

Mid-luteal serum progesterone and estradiol levels as predictors of pregnancy in IVF-ET cycles: May increasing the dosage of progesterone supplementation improve the outcome?

The luteal phase of IVF-ET cycles come under great scrutiny as the cause for the discrepancy between fertilization and pregnancy rates. Under the influence of progesterone and estradiol the endometrium undergoes sequential events including maturation, secretory transformation of the glandular elements, edema formation, vascular proliferation and decidualization of the stroma. Luteal phase support has been shown to be an essential part of ovarian stimulation protocols in IVF program. Conventional luteal support regimens included replacement of progesterone and estradiol in a standard dosage.

Does Anovulation Exist in Eumenorrheic Women?

Past studies have not documented serum progesterone levels in women who supposedly are anovulatory. This study of 550 couples attempting pregnancy aimed at identifying women whose midluteal serum progesterone levels were below the lower limit for ovulation, 15 nmol/L. The study population included 410 women, 74.5% of the total, who were judged to be eumenorrheic and had predictable menstrual cycles of 25 to 35 days without variance of more than 1 day plus or minus. Ovulatory serum progesterone levels exceeding 15 nmol/L were documented in 96.3% of eumenorrheic women. Their mean progesterone level was 38 nmol/L (range, 24-90 nmol/L). These women had a mean age of 32 years. Fifteen eumenorrheic women, 3.7% of the total, appeared to have anovulatory cycles because of a midluteal serum progesterone below 15 nmol/L. Their mean age was 34 years. Four of these 15 women had an isolated erratic cycle. Their menses began more than 14 days after a seemingly appropriately timed sample was taken. Four others did not have appropriately timed sampling and were evaluated in the follicular phase of the cycle. One woman with an initially low progesterone level had a normal level in the following cycle. Two women, both older than 40 years, had increased early follicular levels of follicle-stimulating hormone. One woman conceived in the next cycle. The remaining 3 women were retested in the midluteal phase of 2 or 3 further cycles that appeared to be anovulatory. Midluteal progesterone levels ranged from 9 to 13 nmol/L in all 3 of these women. Only 0.7% of eumenorrheic women in this study had consistently anovulatory menstrual cycles, and serum progesterone levels exceeded the follicular range in all of them. The investigators conclude that anovulation in eumenorrheic women is, at most, infrequent and might be nonexistent except in unusual circumstances. It is important that an appropriately timed serum sample be obtained before labeling a woman as anovulatory.

Inhibin B levels on cycle day 3 to predict the ovulatory response in women with PCOS undergoing ovulation induction via low dose step-up gonadotropin protocol.

In this prospective clinical single blind study, we aimed to investigate whether day 3 serum inhibin B levels in women with polycystic ovarian syndrome(PCOS) are of predictive value for the estimation of the ovarian response to gonadotropins. Ovulation induction with low dose step-up gonadotropin protocol, starting with 75 IU/day, was performed for 30 cycles on 25 patients with PCOS. Day 3 serum inhibin B, follicle-stimulating hormone(FSH) and estradiol, and midluteal serum progesterone levels were measured during each cycle. The correlations between day 3 inhibin B levels and day 3 FSH, day 3 estradiol and midluteal progesterone measurements, as well as the amount of gonadotropin required to provide an ovulatory cycle were investigated. Five (27.8%) out of 18 cycles with day 3 inhibin levels <50.0 pg/ml; and 11 (91.7%) out of 12 cycles with levels > or = 50.0 pg/ml were ovulatory (chi(2)=9.38, p<0.01). Moreover, day 3 inhibin B levels had statistically significant negative correlation with the gonadotropin used; and significant positive correlation with the midluteal progesterone levels (p<0.05). There wasn't any significant relation between day 3 FSH and estradiol levels with the gonadotropin used and progesterone levels. It has been observed that as day 3 serum inhibin B levels increased in women with PCOS, the ovulatory response to gonadotropins and the rate of ovulatory cycles increased significantly.