Mid-luteal Serum Progesterone Research Articles

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.

The definition of unexplained infertility: A systematic review.

There is no consensus on tests required to either diagnose unexplained infertility or use for research inclusion criteria. This leads to heterogeneity and bias affecting meta-analysis and best practice advice. This systematic review analyses the variability of inclusion criteria applied to couples with unexplained infertility. We propose standardised criteria for use both in future research studies and clinical diagnosis. CINAHL and MEDLINE online databases were searched up to November 2022 for all published studies recruiting couples with unexplained infertility, available in full text in the English language. Data were collected in an Excel spreadsheet. Results were analysed per category and methodology or reference range. Of 375 relevant studies, only 258 defined their inclusion criteria. The most commonly applied inclusion criteria were semen analysis, tubal patency and assessment of ovulation in 220 (85%), 232 (90%), 205 (79.5%) respectively. Only 87/220 (39.5%) studies reporting semen analysis used the World Health Organization (WHO) limits. Tubal patency was accepted if bilateral in 145/232 (62.5%) and if unilateral in 24/232 (10.3%). Ovulation was assessed using mid-luteal serum progesterone in 115/205 (56.1%) and by a history of regular cycles in 87/205 (42.4%). Other criteria, including uterine cavity assessment and hormone profile, were applied in less than 50% of included studies. This review highlights the heterogeneity among studied populations with unexplained infertility. Development and application of internationally accepted criteria will improve the quality of research and future clinical care.

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.

Effect of Ubiquinol supplementation on ovulation induction in Clomiphene Citrate resistance

BackgroundClomiphene Citrate is considered the gold-standard for induction of ovulation and has been used for several years to treat PCOS related infertility. Unfortunately, 15-40% of women with PCOS are resistant to Clomiphene Citrate. The study aimed to evaluate potential benefits of adding the active form of Coenzyme Q10 (Ubiquinol) to Clomiphene Citrate compared with Human Menopausal Gonadotropins (hMG) in Clomiphene Citrate resistant PCOS patients. 148 PCOS Patients with Clomiphene Citrate resistance were randomized into two groups (A and B). In group A, controlled ovarian stimulation was done by Clomiphene Citrate 150 mg daily (from 2nd till 6th day of cycle) together with Ubiquinol starting from 2nd day till day of hCG triggering in a dose of 100 mg orally once daily. In group B, hMG was given from 2nd day of the cycle in a dose ranging from 75 to 225 IU. Serial transvaginal ultrasonography was done starting on cycle day 8 and continued till size of leading follicle reaches 18 mm or more then ovulation triggering was done. Thereafter, patients were advised for a timed intercourse (TI) after 36 hours. A blood sample was withdrawn seven days after hCG triggering, for measurement of serum progesterone. If the Patient presented with a missed period for one week, a serum sample was sent for β-hCG.ResultsThere were no statistically significant differences (P > 0.05) between studied groups regarding; number of cases reaching mature follicular size, number of stimulated cycles, endometrial thickness on the day of hCG triggering, mid-luteal serum progesterone, positive serum pregnancy test and clinical pregnancy rate.ConclusionsAddition of Ubiquinol to Clomiphene Citrate improved ovarian responsiveness in Clomiphene Citrate resistant patients with results comparable to conventional hMG stimulation protocol.

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.

The efficacy of vitamin D combined with clomiphene citrate in ovulation induction in overweight women with polycystic ovary syndrome: a double blind, randomized clinical trial.

The aim of this study was to assess the effect of vitamin D supplementation on ovulation rate in overweight subfertile women with PCOS undergoing ovulation induction. This was a single center, parallel-groups, double-blind, and placebo-controlled randomized trial involving 186 eligible women undergoing induction of ovulation with clomiphene citrate (Clomid®, Aventis) 50 mg tablet twice daily starting from the third day of menstrual cycle and for 5 days combined with either oral Vitamin D (ossofortin®, EVA PHARMA) 10,000 IU twice weekly and calcium (calciprex®, Marcyrl Pharmaceutical Industries) 1250 mg twice daily or to receive a placebo with calcium for three successive induction cycles. The vitamin D or placebo supplementation started 1 month before induction cycles (total four cycles). Cycles were monitored with ultrasound follicle tracking and mid-luteal serum progesterone measurement. The primary outcome was the ovulation rate after three induction cycles. The study was performed during the period between January 2018 and September 2018, Eighty six (92.5%) women in the treatment group and 73 (78.5%) in the control group had successful ovulation (p = 0.007). The absolute and relative risk reduction was 14% and 65% respectively. Biochemical and clinical pregnancy occurred in 61.3 and 50.5% in the treatment group, and in 49.5 and 39.8% in the control group (p = 0.105 and 0.141 respectively). In subfertile women with PCOS undergoing induction of ovulation, vitamin D supplementation significantly improved the ovulation rate; however, there was no effect on clinical or biochemical pregnancy.

A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome

To evaluate whether a combination of letrozole and clomiphene citrate (CC) results in higher ovulation rates than letrozole alone in infertile women with polycystic ovary syndrome (PCOS). Open-label randomized controlled trial. Academic medical center using two clinic sites. Women 18-40years of age with a diagnosis of infertility and PCOS as defined by the Rotterdam criteria and no other known cause of infertility. Participants were randomized in a 1:1 ratio, stratified by age and body mass index, to either 2.5mg letrozole alone or the combination of 2.5mg letrozole and 50mg CC daily on cycle days 3-7 for one treatment cycle. Ovulation defined as mid-luteal serum progesterone concentration ≥3ng/mL. Seventy patients were randomized: 35 to letrozole alone and 35 to letrozole and CC. Results were analyzed according to the intention-to-treat principle. Women who received the combination of letrozole and CC had a statistically higher ovulation rate compared with those who received letrozole alone (27 of 35 women [77%] vs. 15 of 35 women [43%]). There were no serious adverse events or multiple-gestation pregnancies in either group. The side-effects profile was similar in the two treatment groups. The combination of letrozole and CC was associated with a higher ovulation rate compared with letrozole alone in women with infertility and PCOS. Further studies are needed to evaluate the effect on live birth rate. NCT02802865.

The impact of luteal serum progesterone levels on live birth rates-a prospective study of 602 IVF/ICSI cycles.

Is the chance of a live birth following IVF treatment and fresh embryo transfer affected by early and mid-luteal serum progesterone (P4) levels? Low as well as high serum P4 levels in the early and mid-luteal phase reduce the chance of a live birth following IVF treatment with fresh embryo transfer. Data from non-human studies and studies of frozen-thawed embryo transfer cycles indicate that low as well as high P4 levels during the mid-luteal phase decrease the chance of pregnancy. The altered P4 pattern may disrupt the endometrial maturation leading to asynchrony between embryonic development and endometrial receptivity, thereby, compromising implantation and early development of pregnancy. Prospective multicenter cohort study of 602 women undergoing IVF treatment. Patients were recruited from four Danish public Fertility Centers from May 2014 to June 2017. The study population was unselected, thus, representing a normal everyday patient cohort. Patients were treated in a long GnRH-agonist protocol or a GnRH-antagonist protocol and triggered for final oocyte maturation with either hCG or a GnRH-agonist. The same vaginal luteal support regimen was applied in all patients. Serum P4 levels from the early or mid-luteal phase were correlated to positive hCG and live birth rates (delivery > gestational week 20). Patients were divided into four P4 groups based on raw data of P4 serum levels and reproductive outcomes during early luteal phase (P4<60 nmol/l, P4 60-100 nmol/l, P4 101-400 nmol/l and P4>400 nmol/l) and during mid-luteal phase (P4<150 nmol/l, P4 150-250 nmol/l, P4 251-400 nmol/l and P4>400 nmol/l). The optimal chance of pregnancy was achieved with serum P4 levels of 60-100 nmol/l in the early luteal phase whereas the optimal P4 level during the mid-luteal phase was 150-250 nmol/l. Below, but most distinctly above these levels, the chance of pregnancy was consistently reduced. With an early luteal P4 level of 60-100 nmol/l, the chance of a positive hCG-test was 73%, 95% CI: [59, 84] following cleavage stage embryo transfer. In contrast, with P4 levels >400 nmol/l, the chance of a positive hCG-test was significantly reduced to 35%, 95% CI: [17, 57], thus, an absolute risk difference of -38%, P = 0.01. A similar negative association between early luteal P4 and live birth rate was found, although it did not reach statistical significance. During the mid-luteal phase, a P4 level of 150-250 nmol/l resulted in an optimal chance of live birth: 54%, 95% CI: [37, 70] compared to 38%, 95% CI: [20, 60] with a P4 level >400 nmol/l, thus, an absolute risk difference of -16%, P = 0.14. All estimates were adjusted for maternal age, maternal BMI, study site, final follicle count and late follicular P4 levels. This study is the first to explore the possible upper and lower thresholds for luteal P4 following IVF treatment and fresh embryo transfer, and the optimal P4 ranges found in this study should be corroborated in future clinical trials. Furthermore, the P4 thresholds in this study only apply to fresh IVF cycles, using vaginal luteal phase support, as the optimal P4 level in cycles using intramuscular P4 may be different. Future studies are necessary to explore whether additional exogenous luteal P4 supplementation in the low P4 group could increase the chance of a live birth following fresh embryo transfer, and whether patients with luteal P4 levels >400 nmol/l would benefit from segmentation followed by subsequent transfer in frozen/thawed cycles. NCT02129998 (Clinicaltrials.gov). L.H.T. received an unrestricted grant from Ferring Pharmaceuticals, Denmark, to support this study. P.H. received unrestricted research grants from MSD, Merck, Gedeon Richter and Ferring Pharmaceuticals outside of this work as well as honoraria for lectures from MSD, Merck and Gedeon Richter outside of this work. U.K. received honoraria for lectures from MSD and Ferring Pharmaceuticals outside of this work. C.A. received unrestricted research grants from MSD, IBSA, and Ferring Pharmaceuticals outside of this work as well as honoraria for lectures from MSD and IBSA. H.O.E. and B.B.P. received an unrestricted research grant from Gedeon Richter outside of this work. K.E., L.B., D.P. and B.H. have no conflict of interest. Furthermore, grants from 'The Health Research Fund of Central Denmark Region', 'The Research Foundation of the Hospital of Central Jutland', 'The Research Foundation of A.P. Møller', 'The Research Foundation of Aase & Ejnar Danielsen', 'The Research Foundation of Dagmar Marshall', 'The Research Foundation of Dir. Jacob Madsen & Hustru Olga Madsen', 'The Research Foundation of Fam. Hede Nielsen' and 'The Danish Medical Research Grant' supported conducting this study. The providers of funding were neither involved in the conduction of the study nor in the writing of the scientific report.

Daytime Variation in Serum Progesterone During the Mid-Luteal Phase in Women Undergoing In Vitro Fertilization Treatment.

To investigate whether mid-luteal serum progesterone (P4) exhibits significant fluctuations during a 12-h daytime period in women undergoing in vitro fertilization (IVF) and to explore whether the extent of these fluctuations could impact the interpretation of luteal progesterone levels in a clinical setting. Explorative pilot study. Public hospital-based fertility unit. Ten women undergoing IVF treatment. Seven days after oocyte pick-up, patients underwent frequent repeated blood sampling (every 60 min for 12 h and during two of these hours, every 15 min). Serum samples were analyzed for progesterone, estradiol, and luteinizing hormone (LH). Daytime fluctuations in s-progesterone and s-estradiol. There was a significant positive correlation between median P4 levels and the magnitude of P4 variations-women with median P4 < 60 nmol/l had clinically stable P4 levels throughout the day, while patients with median P4 > 250 nmol/l exhibited periodic P4 peaks of several hundred nanomoles per liter. These endogenous P4 fluctuations were observed irrespective of the type of stimulation protocol or mode of triggering of final oocyte maturation and despite the fact that LH was under the detection limit at the time of measurement. Simultaneously, large fluctuations were seen in s-estradiol. Monitoring of early to mid-luteal P4 levels in IVF cycles may be valuable in the planning of individualized luteal phase support in the attempt to increase reproductive outcomes. The prerequisite for luteal phase monitoring is, however, that the validity of a single measured P4 value is reliable. We show for the first time, that a single P4 measurement in the low progesterone patient quite accurately reflects the corpus luteum function and that the measurement can be used to detect IVF patients with a need of additional exogenous luteal P4 administration.

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.

Midluteal Serum Estrogen and Progesterone Levels predict Pregnancy Rate in in vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: A Prospective Study

ABSTRACTIntroductionIn assisted reproduction technique cycles, controlled ovarian stimulation (COS) leads to supraphysiological levels of steroid hormone secretion and the subsequent need for luteal phase support (LPS). Therefore, existing data on the steroid secretion profile in the luteal phase of spontaneous conception cycles and its predictive value for pregnancy outcome need to be discussed against the background of preceding COS. The clinical significance of luteal phase hormones, such as estrogen (E2) and progesterone (P4), in predicting pregnancy after controlled ovarian hyperstimulation protocols forin vitrofertilization (IVF) or intracytoplasmic sperm injection (ICSI) is still poorly understood. The aim of the present study was to investigate the role of midluteal serum E2 and P4 level in predicting successful pregnancy in patients undergoing IVF/ICSI.Materials and methodsOne hundred fifteen women were recruited for the study. They were given gonadotropin-releasing hormone antagonist protocol and human chorionic gonadotropin (hCG) was administered if at least three follicles were more than 18 mm in size. Transvaginal ultrasound-guided oocyte retrieval followed by ICSI and embryo transfer (ET) was done. Post-ET, all women had same LPS. The E2 and P4 measurements were done at day of ET (day 0) and 9 days post-ET (day 9). Levels of E2 and P4 were compared between those who subsequently became pregnant and those who could not achieve pregnancy. Statistical analysis was performed using Statistical Package for the Social Sciences.ResultsForty-six (40%) achieved pregnancy. The E2 and P4 levels on day 9 were significantly higher in those who achieved pregnancy (p &lt; 0.01). Out of 46 pregnancies, 38 were ongoing viable pregnancies.ConclusionLuteal phase E2 and P4 can be used as prognostic marker to predict pregnancy in IVF/ICSI cycles.How to cite this articleNigam S, Joy I, Shankar K, Varma TR. Midluteal Serum Estrogen and Progesterone Levels predict Pregnancy Rate inin vitroFertilization/Intracytoplasmic Sperm Injection Cycles: A Prospective Study. Int J Infertil Fetal Med 2017;8(2):50-53.

Peri-ovulatory Phytoestrogen Improves Pregnancy Rate in Women with Polycystic OvarianSyndrome Receiving Ovulation Induction with Clomiphene Citrate

Background: PCOS is the most common ovarian factor of female infertility, in low resource countries clomiphene citrate is the most popular drug used for induction of ovulation as its price is affordable for most of patients with least side effects. Objective: Evaluate the effect of phytoestrogen in women receiving induction with clomiphene citrate when given peri ovulatory to oppose antiestrogenic effect of clomiphene citrate. Methodology: Prospective study conducted on 500 patients with PCOD who attended infertility clinic, patients were randomized into 2 groups both groups received traditional CC induction , group (1) 225 patients received phyto-estrogen, starting in the 7th day of the cycle till the day of HCG injection ,group(2) 225 patients received clomiphene citrate only. Endometrial thickness and follicular growth were assessed by transvaginal US. When follicles reached 18 mm, 10,000 IU HCG was administered together with timed intercourse. Both groups were compared as regard cumulative pregnancy rate, ovulation, endometrial thickness and change in hormonal milieu. Results: Midluteal serum progesterone was significantly higher in the study group as compared with the control group (15.93 ±1.8 versus 12.93 ± 1.8); endometrial thickness was also greater in the study group as compared with the control group, (10.3 ± 1.1 versus 8.2 ± 0.9). Ovulation in the three cycles was in favor of study group 82.5% versus 80.4% but not statistically significant. The CPR was significantly higher in the study group than in the control group (34.2% vs. 20.8%. P = 0.1). There were 6 cases of multiple pregnancy in the study group and 4 cases in the control group. Conclusion: Adding phytoestrogen to CC induction improve ovulation and pregnancy rate, it is a good option for patients with PCOS seeking for pregnancy treatment with affordable price and minimal side effects

Follicular phase dexamethazone administration in polycystic ovarian syndrome patients who are clomiphene citrate resistant

Aim of the workTo compare the effect of adding short course follicular phase dexamethazone to clomiphene citrate versus increasing clomiphene citrate dose in cases of resistance. Materials and methodsThe study was conducted on 85 with polycystic ovary syndrome who were resistant to 150mg clomiphene citrate daily for 5 days for 3 months and were attending El Shatby Maternity University Hospital in the period between September 2011 and May 2013. These patients were randomly allocated by closed envelope method into one of the two groups: Group I: 44 patients received 200mg daily of clomiphene citrate from day 3 and for 5 days together with 2mg dexamethazone daily from day 3 and for 10 days. Group II: 41 patients received 200mg daily of clomiphene from day 3 and for 5 days. ResultsWe found that a significant higher rate of ovulation was reported in the dexamethazone group compared to clomphine citrate only group, endometrial thickness was more favorable in dexamethazone group than the other group, mid luteal serum progesterone was a higher level in dexamesathone group compared to the other group and serum pregnancy rate was higher in dexamethazone group than the other group. ConclusionAlthough the mechanism underlying the beneficial effects of dexamesathone is not exactly understood, it is apparent from our data that dexamesathone therapy during the follicular phase can enhance follicular development and ovulation. Dexamethazone (corticosteroids) therapy combined with clomphine citrate can improve folliculogenesis, ovulation, and pregnancy rate in clomphine citrate resistant polycystic ovary syndrome.

Mid-luteal serum progesterone concentrations govern implantation rates for cryopreserved embryo transfers conducted under hormone replacement

This study explores the relevance of mid-luteal serum hormonal concentrations in cryopreserved embryo transfer cycles conducted under hormone replacement therapy (HRT) control and which involved single-embryo transfer (SET) of 529 vitrified blastocysts. Widely ranging mid-luteal oestradiol and progesterone concentrations ensued from the unique HRT regimen. Oestradiol had no influence on clinical pregnancy or live birth rates, but an optimal progesterone range between 70 and 99 nmol/l (P < 0.005) was identified in this study. Concentrations of progesterone below 50 nmol/l and above 99 nmol/l were associated with decreased implantation rates. There was no clear interaction between oestradiol and progesterone concentrations but embryo quality grading did show a significant influence on outcomes (P < 0.001 and P = 0.002 for clinical pregnancy and live birth rates, respectively). Multiple comparison analysis showed that the progesterone effect was influential regardless of embryo grading, body mass index or the woman's age, either at vitrification or at cryopreserved embryo transfer. The results support the argument that careful monitoring of serum progesterone concentrations in HRT-cryopreserved embryo transfer is warranted and that further studies should explore pessary adjustments to optimize concentrations for individual women to enhance implantation rates.