Serum Progesterone Measurement Research Articles

Sugammadex Use for Reversal in Nonobstetric Surgery During Pregnancy: A Reexamination of the Evidence.

Sugammadex Use for Reversal in Nonobstetric Surgery During Pregnancy: A Reexamination of the Evidence.

Effect of prolidase on the development of varicose veins in pregnant women

Introduction and Aim: Varicose veins are more common during pregnancy and, if left untreated, can cause venous insufficiency and edema in the legs. Women have venous insufficiency both before and after pregnancy. According to research, the cytosolic metalloproteinase prolidase regulates the breakdown of collagen and other proteins in the extracellular matrix. Prolidase deficiency, which impairs the enzyme's normal function, has severe clinical manifestations. The objective of this study is to discover how the enzyme prolidase influences the development of varicose veins in pregnant women.
 
 Materials and Methods: This study included approximately 70 women aged 25-45 years who were pregnant in their third trimester. The participants were assigned to two groups based on diagnosis of having varicose veins (n=40) and those without (n=30). Quantitative measurements of serum progesterone and prolidase concentrations were made. Data collected was subjected to statistical analysis.
 
 Results: Varicose veins were prevalent in 57.14% of the pregnant women, the severity of which increased with age. The mean blood concentrations of progesterone and prolidase levels were higher in pregnant women with varicose veins in comparison to controls.
 
 Conclusion: Chronic venous insufficiency and mild varicose veins are more common in pregnant women aged 40 years and above. An increased level of progesterone and prolidase enzyme in serum was seen to be associated with chronic varicose insufficiency in pregnant women.

Validation of a fully automated chemiluminescent immunoassay for cattle serum and plasma progesterone measurement.

Monitoring circulating progesterone concentration ([P4]) is an important component of basic and applied reproduction research and clinical settings. IMMULITE® 2000 XPi (Siemens Healthineers, Cary, NC) is a newly upgraded fully automated immunoassay system marketed for human use to measure concentrations of different measurands including P4. Our objective was therefore to characterize the analytical performance of the IMMULITE® 2000 XPi P4 immunoassay (IPI) across the reportable range in serum and plasma of cattle. The IPI validation protocols included characterization of the method linearity, within-run, and between-run precision through calculation of the coefficient of variation (CV). The method accuracy was assessed through the calculation of the spiking-recovery (SR) bias across the reportable range (0.2-40.0 ng/mL). Passing-Bablok regression and Bland-Altman plots were used to determine the interlaboratory bias for two laboratories. Three types of observed total error (TEo) were calculated based on the considered type of bias, TEoSR (spiking-recovery), TEoRB (range-based bias), and TEoAB (average-based bias). The IPI was linearly related to the true value (R 2 = 0.997) across the reportable range. The within-run and between-run precision (CV%) of the IPI for both serum and plasma [P4] of clinical relevance (1, 2, 5, and 10 ng/mL) were <5 and <10%, respectively. The TEo reported here for serum and plasma at [P4] of 1 and 5 ng/mL was ~20 and 25%, respectively. Of interest, the three types of TEo were relatively similar regardless of the considered bias. We concluded that the automated IPI provides a precise, accurate, reliable, and safe method for measuring [P4] in both serum and plasma of cattle. Consistent with the manufacturer's recommendations, the serum matrix is more accurate than plasma.

Do serum progesterone levels on the day prior to Day 5 Embryo transfer influence pregnancy outcome in artificial frozen-thaw embryo transfer cycle?

Background: Progesterone (PG) is an essential hormone in the process of implantation and pregnancy maintenance. Frozen-thawed embryo transfer (FET) is being performed worldwide. This study was designed to investigate whether serum progesterone levels on the day prior to day 5 frozen-thawed embryo transfer (FET) to hormonally prepared endometrium correlates with pregnancy outcomes. Materials and Methods: A single center longitudinal observational study was conducted at an infertility center over a period of three months from October 2022 to December 2022. The study participants were the patients attending the infertility center who satisfied the inclusion and exclusion criteria. A total of 30 participants were included in this study. Serum progesterone levels were measured on the day of starting the progesterone (P0) and on day four (P4), the day prior to embryo transfer. Data analysis was conducted using SPSS version 21. Results: The mean (SD) age in those who had positive pregnancy outcome was 34.22 (1.26) years and in those who had negative pregnancy outcomes was 39.92 (2.11) years and the difference was significant (P = 0.001). The mean (SD) serum progesterone levels in those who had positive pregnancy outcome at day 0 was found to be 0.61 (1.19) ng/ml and in those who had negative pregnancy outcomes was 0.28 (0.27) ng/ml but, the difference was not significant (P = 0.347). The mean (SD) serum progesterone levels in those who had positive pregnancy outcome at day 4 was found to be 10.84 (8.13) ng/ml and in those who had negative pregnancy outcomes was 8.13 (3.81) ng/ml and the difference was significant (P = 0.039). Conclusion: Pregnancy loss increases with age and serum progesterone measurements at day 4 prior to embryo transfer could be used to assess pregnancy outcomes in frozen-thawed embryo transfer (FET) technique of infertility treatment. Monitoring of serum PG levels can be done for diagnosing potential luteal support defects before performing FET with artificial cycle (AC).

In vivo embryo development in bitches inseminated laparoscopically after ovulation time estimated based on a single progesterone determination.

Logistic and economical limitations are often the causes of dog owners not accurately monitoring the estrous cycle and the optimal insemination time. The aim of this study was to evaluate in vivo early embryonic development in bitches, after the analysis of sequential vaginal cytologies associated to single progesterone measurement and single laparoscopic insemination with high quality semen (fresh and with high spermatozoa concentration) or low-quality semen (frozen/thawed and with low spermatozoa concentration) at 48 h post- ovulation time predicted on a single progesterone measurement. Ten bitches were inseminated with 250 x 106 fresh spermatozoa (80% motility), and ten with 80 x 106 frozen/thawed spermatozoa (60% motility) in the cranial part of each uterine horn. Seven days later, ovariohysterectomy was performed and the oviducts and uterine horns and body were flushed to recover embryos and unfertilized oocytes. In 80% of the bitches inseminated with fresh and 50% of bitches inseminated with frozen/thawed semen, embryos at 2 to 8 cells stage were recovered mostly from the, oviducts. This study indicates that pregnancies can be obtained with a single laparoscopic intrauterine insemination after single serum progesterone measurement, although with a low number of embryos. This result should be taken into account in case economic or logistic restrictions that affect the possibility of owners to plan an accurate monitoring of the optimal breeding time using fresh and frozen semen.

The addition of dydrogesterone improves the outcomes of pregnant women with low progesterone levels when receiving vaginal progesterone alone as luteal support in HRT-FET cycles.

Vaginal progesterone (VP) alone has been used as luteal support (LS) in HRT-FET cycles without measuring serum progesterone concentrations (SPC) because it can achieve adequate intrauterine progesterone levels. However, several reports showed that the co-administration of progestin produced better outcomes than VP alone. We tried to address this discrepancy, focusing on SPC. VP was given to 180 women undergoing HRT-FET. We measured SPC when pregnancy was diagnosed on day 14 of LS. We compared assisted reproductive technology outcomes between VP alone versus VP + dydrogesterone (D). When using VP alone, average SPC in the miscarriage cases (9.6ng/mL) were significantly lower compared with the ongoing pregnancy (OP) cases (14.7ng/mL). The cut-off value for progesterone, 10.7ng/mL, was a good predictor for the subsequent course of the pregnancy. Of 76 women receiving D ± VP from the start of LS and achieving a pregnancy, the numbers of OP were 44 (84.6%) in SPC≥ 10.7ng/mL and 20 (83.3%) in SPC ≤ 10.7ng/mL with no significant difference. VP alone resulted in lower SPC in some pregnant women in HRT-FET cycles and exhibited a lower OP rate. The co-administration of D improved an OP rate of low progesterone cases to the level comparable with non-low progesterone cases.

Serum Progesterone Concentration and Ongoing Pregnancy Rate in Frozen-Thawed Embryo Transfers with Intramuscular Plus Vaginal Progesterone Administration for Endometrial Preparation

Background: Insufficient serum progesterone level in the implantation phase may reduce the rate of pregnancy during freeze embryo transfer (FET) cycles. The present study aimed to evaluate the impact of FET day serum progesterone level on pregnancy outcomes in patients receiving intramuscular plus vaginal progesterone administration for endometrial preparation. Methods: Based on serum progesterone level on FET day, patients were divided into four quartiles: first (&lt;25%), second (26–50%), third (51%–75%), and fourth (&gt;75%). There was no significant difference among groups in basal characteristics. Results: No statistically significant difference was seen among groups concerning the mean number of retrieved and mature oocytes, embryos transferred, and endometrial thickness (EnT). The rate of implantation (P=0.5), biochemical (P=0.75), clinical (P=0.54), and ongoing pregnancy (P=0.5) were not associated with serum progesterone level on embryo transfer day. Conclusion: We found that there is no association between serum progesterone level on ET day and pregnancy outcome during FET cycles. It seems that combination therapy using intramuscular and vaginal progesterone, keeps the serum progesterone on ET day high enough that eliminates the need for serum progesterone measurement.

Is there an optimal window of time for transferring single frozen-thawed euploid blastocysts? A cohort study of 1170 embryo transfers.

Is there an optimal window of time when the transfer of single frozen-thawed euploid blastocysts is associated with a maximal live birth rate (LBR)? Performing a single frozen-thawed euploid blastocyst transfer at 160 ± 4 h post-hCG trigger in modified-natural frozen-thawed embryo transfer (FET) cycles was independently associated with a higher LBR as compared to transfers outside this window; however, in natural FET cycles, LBRs were comparable across a wider range of time intervals. There is compelling evidence for maintaining embryo-endometrial synchrony to optimize clinical outcomes following FETs, which could potentially be achieved by matching the transfer time of an embryo post-ovulation to its developmental age post-oocyte retrieval. For modified-natural cycles, ovulation is widely accepted to occur ∼40 h following the hCG trigger, whilst ovulation following spontaneous LH surge onset is thought to vary from 24 to 56 h. This is a multicentered retrospective cohort study analyzing 1170 single frozen-thawed euploid blastocyst transfers following trophectoderm biopsy and preimplantation genetic testing (PGT) between May 2015 and February 2019. Limiting the analysis to single euploid embryo transfers allowed for a more accurate estimation of the endometrial synchrony factor by controlling for the developmental stage of the embryo (full blastocyst or more advanced) and its genetic composition. LBR per FET was the primary outcome measure. Patients underwent natural or gonadotrophin-induced preparation of the endometrium, with serial serum oestradiol, LH and progesterone measurements. Optimally timed transfers were predefined as those conducted 120 ± 4 h post-ovulation since biopsy and subsequent cryopreservation of full blastocysts which is usually performed at 116-124 h post-oocyte retrieval. This was considered the equivalent of 160 ± 4 h post-hCG trigger in modified-natural cycles (n = 253), as ovulation was assumed to occur ∼40 h after the hCG trigger. For natural cycles (n = 917), this was also considered to be, on average, 160 ± 4 h post the spontaneous LH surge. Thus, study groups were determined as those with optimal timing or not, and additional exploratory and subgroup analyses were performed, varying the time window in terms of onset and width, both overall and per endometrial preparation protocol. Statistical analysis was performed using the generalized estimating equations (GEE) framework to control for the clustered nature of the data while adjusting for potential confounders. Overall, LBRs were significantly higher when the transfer had been performed at 160 ± 4 h post-hCG trigger or LH surge onset compared to when it had been performed outside this window (44.7% vs 36.0%; P = 0.008). A multivariable regression GEE model including the cycle type (natural versus modified-natural), previtrification embryo quality (top versus good quality), embryo stage (fully hatched versus hatching or earlier blastocyst), vitrification day (D5 versus D6) and survival rate (>90% versus <90%) as covariates, confirmed that, overall, embryo transfers conducted 160 ± 4 h post-hCG trigger or LH surge onset (the assumed equivalent of 120 ± 4 h post-ovulation) were associated with a significantly higher LBR (relative risk (RR) 1.21, 95% CI 1.04-1.41). Subgroup exploratory analyses per endometrial preparation protocol demonstrated that these findings were primarily present in the modified-natural cycle group (RR 1.52, 95% CI 1.15-1.99), whilst the natural cycle group showed comparable LBRs across a wider range of time intervals. Moreover, the overall LBR for the natural group (36.8%; 95% CI 33.7-39.9%) was lower than that of the modified-natural group (41.3%; 95% CI 35.4-47.1%), suggesting that there likely remains a greater potential to further optimize the timing of natural cycle embryo transfers. As with all retrospective studies, the presence of residual unknown bias cannot be excluded. Additionally, patients included in this study were a selected group who underwent PGT for specific reasons and hence the results obtained might not be directly applicable to the general population or embryos that have not undergone embryo biopsy. Furthermore, the criteria utilized to interpret hormonal data from natural cycles were specifically adopted for the present study and need to be validated in further studies. The results of this study highlight the significance of embryo-endometrial synchrony for the optimization of frozen embryo transfer outcome. However, it also clearly supports that the implantation window is in most cases wide and the achievement of live birth is possible with relatively high success rates even outside the optimal window of 160 ± 4 h post-trigger for modified-natural cycles and across a range of time intervals for natural cycles. Additionally, this study suggests that implantation rates could be further optimized in natural cycles by improving methods of assessing embryo-endometrial synchrony. C. V. is supported by a National Health and Medical Research Council Early Career Fellowship (GNT1147154). No other funding was received for this study and there are no competing interests. N/A.

Post-mating diclofenac vs. carprofen treatment on serum progesterone levels and reproductive outcomes in Hungarian-Merino ewes during the non-breeding season.

The maternal recognition process is crucial for the establishment of healthy pregnancy. In this process, anti-luteolytic applications are one of the main reproductive strategies to manage the embryonic losses and maximize reproductive profitability in farm animals. The aim of this study was to investigate the efficacy of post-mating NSAID treatments on reproductive parameters (pregnancy rate, lambing rate, multiple birth rate, litter size) and serum progesterone levels in ewes stimulated with progesterone non-breeding season. For this purpose, two different experiments (diclofenac and carprofen) were conducted in the same ewe flock induced with short-term progestogen-based protocol in the non-breeding season for two consecutive years. In experiment 1 (n=85), 42 ewes were injected with 2.5mg/kg diclofenac on the 9th and 10th days post-mating, and the rest were not treated and served as control. In experiment 2 (n=82), 40 ewes were injected with 1.4mg/kg carprofen on the 9th days post-mating, and the rest were not treated as control. In both experiments, blood samples were collected from all ewes on days 9, 12 and 13 post-mating to measure serum progesterone levels. In both experiments, there were no differences both reproductive parameters and serum progesterone levels when compared to the control groups. It was concluded that post-mating diclofenac and carprofen treatments in the critical period have no significant effects on both reproductive parameters and serum progesterone levels in ewes in the non-breeding season.

Progesterone supplementation in natural cycles improves live birth rates after embryo transfer of frozen-thawed embryos-a randomized controlled trial.

STUDY QUESTIONDoes supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles improve the live birth rate?SUMMARY ANSWERSupplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles significantly improves the number of live births.WHAT IS KNOWN ALREADYProgesterone supplementation during luteal phase and early pregnancy may improve the number of live births after frozen-thawed embryo transfer. However, due to the limited number of previous studies, being mainly retrospective, evidence is still limited.STUDY DESIGN, SIZE, DURATIONThis is a prospective randomized controlled trial, performed at two university clinics. In total, 500 subjects were randomized with a 1:1 allocation into two groups, during the period February 2013 to March 2018. Randomization was performed after a frozen embryo transfer in a natural cycle by use of opaque sealed envelopes. The primary outcome was live birth rate; secondary outcomes were pregnancy, biochemical pregnancy, clinical pregnancy and miscarriage rate, and if there was a possible association between the serum progesterone concentration on the day of embryo transfer and live birth rate.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen, receiving embryo transfer in natural cycles participated in the study. The embryos were frozen on Day 2, 3, 5 or 6. In total, 672 women having regular menstrual cycles were invited to participate in the study; of those, 500 agreed to participate and 488 were finally included in the study. Half of the study subjects received progesterone supplementation with progesterone vaginal tablets, 100 mg twice daily, starting from the day of embryo transfer. The other half of the subjects were not given any treatment. Blood samples for serum progesterone measurements were collected from all subjects on the day of embryo transfer.MAIN RESULTS AND THE ROLE OF CHANCEThere were no differences in background characteristics between the study groups. In the progesterone supplemented group, 83 of 243 patients (34.2%) had a live birth, compared to 59 of 245 patients (24.1%) in the control group (odds ratio 1.635, 95% CI 1.102–2.428, P = 0.017*). The number of pregnancies was 104 of 243 (42.8%) and 83 of 245 (33.9%), respectively (odds ratio 1.465, 95% CI 1.012–2.108, P = 0.049*) and the number of clinical pregnancies was 91 of 243 (37.4%) and 70 of 245 (28.6%), respectively (odds ratio 1.497, 95% CI 1.024–2.188, P = 0.043*). There were no significant differences in biochemical pregnancy rate or miscarriage rate. There was no correlation between outcome and serum progesterone concentration.LIMITATIONS, REASONS FOR CAUTIONThe study was not blinded because placebo tablets were not available. Supplementation started on embryo transfer day, regardless of the age of the embryos, which resulted in a shorter supplementation time for Day 5/6 embryos compared to Day 2/3 embryos.WIDER IMPLICATIONS OF THE FINDINGSSupplementation with progesterone in natural cycles improved the number of live births after frozen-thawed embryo transfer and should therefore be considered for introduction in clinical routine.STUDY FUNDING/COMPETING INTEREST(S)The study was funded by Uppsala University, the Uppsala-Family Planning Foundation, and Ferring Pharmaceuticals AB, Malmö, Sweden. The authors have no personal conflicting interests to declare.TRIAL REGISTRATION NUMBERNL4152.TRIAL REGISTRATION DATE5 December 2013.DATE OF FIRST PATIENT’S ENROLMENT18 February 2013.

The use of alfaxalone for short-term anesthesia can confound serum progesterone measurements in the common marmoset: a case report.

Alfaxan® (alfaxalone) is a steroid general anesthetic widely used in veterinary medicine for induction and maintenance of anesthesia in several species. While the use of alfaxalone in veterinary practice has several benefits compared to the use of other anesthetic agents, the fact that it is derived from progesterone may confound the measurement of the latter in the blood of animals under alfaxalone treatment. In the present case study, we report the measurement of serum progesterone in an individual common marmoset (Callithrix jacchus) during five ovarian cycles in which luteolysis was induced by PGF2. Blood samples were usually taken from the awake animal with the exception of the fifth cycle in which the sample was collected under alfaxalone anesthesia in connection with a tooth extraction. In contrast to the previous four cycles in which luteolysis resulted in the expected marked decrease in progesterone concentrations, the – apparent – progesterone level in the cycle under alfaxalone treatment remained unexpectedly high. Cross-reactivity of the non-specific antibody used in the progesterone assay with alfaxalone most likely explains this finding.

P-612 Current understanding of polycystic ovary syndrome (PCOS) and potential interest in future trial to evaluate role of myo-inositol as ovulation induction agent – Stakeholder’s surveys

Abstract Study question To assess awareness amongst consumers and gynaecologists on various aspects of PCOS and to explore the willingness to participate in a future trial of myo-inositol as an ovulation induction agent. Summary answer Significant lack of awareness on various aspect of PCOS amongst consumers is concerning. Gynaecologists and consumers are keen on trial exploring myo-inositol in anovulatory PCOS. What is known already Initial studies have reported that Myo-inositol can increase the frequency of menstruation and ovulation along with benefit with androgenic and glycaemic parameters in women with PCOS. There is a need for large, well designed and powered randomised controlled trial to evaluate the role of Myo-inositol as a fertility enhancing agent on its own and as an adjunct to clomiphene/letrozole in women with anovulatory PCOS. There has been a growing interest in patient and public involvement in setting research priorities to reduce the risk of discrepancy between what stakeholder’s experience as important unanswered questions and those which are actually researched. Study design, size, duration The surveys were hosted using on-line survey tool (www.surveymonkey.com) between Dec 2020 and April 2021, in the UK. Bespoke questionnaires were designed for the survey of gynaecologists (comprising of 27 questions) and the women with PCOS (comprising of 20 questions). These were peer reviewed and included, multiple choice questions, questions with a Likert scale response and open format questions. Ethical approval was provided by Queen Mary University of London (QMUL) ethics committee (Ref: QMERC2014/76). Participants/materials, setting, methods The online clinician survey was a cross sectional study of gynaecologists who look after women with PCOS, and the consumer survey was a cross sectional study of the members of PCOS support organisation “Verity”. The data was collected using on-line survey tool and was summarised descriptively using numbers and percentages. For the descriptive statistics, we used absolute and relative frequencies, and we also used the median and the IQR to detect the most common answers. Main results and the role of chance There were 244 responses; 104 gynaecologists and 140 consumers. Majority of the consumers were aware that, women with PCOS struggle with irregular cycles (94%); to loss/maintain weight (83%); and to conceive (85%). 81% were aware of risk of subfertility, however, only half were aware of risks associated with irregular menstrual cycles (51%), gestational diabetes (57%) and long-term risks such as diabetes (62%). 96% felt subfertility was an important issue, however, only 2/5th were aware of treatment options, a third were aware of need for USS monitoring whilst taking clomid tablets and that clomid tablets can only be used for 6-12 cycles. The clinician survey showed that 70% of the gynaecologists chose life-style measurements for the first line option and the second line options were 35% for clomiphene, 29% for clomiphene + metformin, followed by 21% for letrozole. 79% use USS to confirm ovulation and 60% by measuring serum progesterone; 37% monitor all cycles of ovulation induction whereas 41% monitor index cycle. Two thirds of the gynaecologists (72%) and majority of consumers (88%) agreed on the need to research myo-inositol for ovulation induction in PCOS and were willing to participate in such a study. Barriers for recruitment and retention were also explored. Limitations, reasons for caution Clinician survey was unable to get the views of general practitioners and endocrinologists, who might have a different perspective particularly on non-reproductive outcomes. Consumer survey was online survey in English which can result in a selection bias and the views of women from other socio-economic and cultural backgrounds may differ. Wider implications of the findings These surveys provide vital information in planning a definitive RCT on the role of myo-inositol in women with anovulatory PCOS trying to conceive. Further research tools need to be explored to provide better information and education to the women with PCOS particularly on the long-term risks associated with PCOS. Trial registration number NA

P-660 Polymorphisms in FSHR gene do not affect late follicular phase steroidogenic response in predicted normoresponders. Secondary analysis of a prospective multicenter cohort study

Abstract Study question Does the presence of FSHR SNPs influence late follicular phase progesterone and estradiol serum levels in predicted normoresponders treated with rFSH? Summary answer The presence of FSHR SNPs (rs6165, rs6166, rs1394205) had no statistically significant impact on late follicular phase serum progesterone and estradiol levels. What is known already Previous studies have shown that late follicular phase serum progesterone and estradiol levels are significantly correlated with the magnitude of ovarian response. Several authors have proposed that individual variability in the response to ovarian stimulation could be explained by variants in FSHR. So far, the literature is scarce on the influence of this genetic variability on late follicular phase steroidogenic response. Our aim is to determine whether genetic variants in the FSHR gene could modulate late follicular phase serum progesterone and estradiol levels. Study design, size, duration We performed a secondary analysis of a multicenter multinational prospective study including 366 patients from Vietnam, Belgium and Spain (166 from Europe and 200 from Asia), conducted from 11/2016-06/2019. All patients underwent ovarian stimulation followed by oocyte retrieval in an antagonist protocol with a fixed daily dose of 150IU rFSH. All patients had a serum progesterone and estradiol measurement on the day of trigger and were genotyped for 3 FSHR SNPs (rs6165, rs6166, rs1394205). Participants/materials, setting, methods Patients included were predicted normal responder women &amp;lt;38 years old undergoing their first or second ovarian stimulation cycle. The prevalence of late follicular phase elevated serum progesterone (EP), as well as mean serum progesterone and estradiol levels on the day of trigger were compared between the different FSHR SNPs genotypes. EP was defined as &amp;gt; 1.5 ng/ml. Main results and the role of chance The overall prevalence of EP was 15.8% (n = 58). No significant difference was found in the prevalence of EP in Caucasian and Asian patients (17.5% vs. 14.5%). Genetic model analysis revealed a similar prevalence of EP in co-dominant, dominant and recessive models for variants FSHR rs6166, rs6165 and rs1394205. Also, no statistically significant difference was found in the mean serum progesterone levels in the three genetic models. Likewise, FSHR SNPs genotypes had no statistically significant impact in the mean late follicular phase serum estradiol levels Limitations, reasons for caution This study is a post-hoc analysis of a multicenter multinational prospective cohort study. The results must be interpreted with caution considering the sample size of the EP group. The fact that a fixed daily dose of 150 IU rFSH was used in this population precludes the generalization of the results. Wider implications of the findings Based on our results, FSHR SNPs rs6165, rs6166, rs1394205 do not influence late follicular phase serum progesterone nor estradiol levels in predicted normal responders. These findings add to the controversy in the literature regarding the impact of individual genetic susceptibility in response to ovarian stimulation in this population. Trial registration number not-applicable

A phase 3 study to determine the breast cancer risk reducing effect of denosumab in women carrying a germline BRCA1 mutation (BRCA-P Study).

TPS10616 Background: Women with BRCA1 mutations have a 50-70% lifetime risk of developing breast cancer. Currently, prophylactic mastectomy is the only strategy that significantly reduces breast cancer risk. Recent evidence suggests that the RANK/RANKL signaling pathway plays a pivotal role in the development of BRCA1-mutated tumors. Targeting the RANK pathway has been shown to attenuate breast epithelial proliferation in vitro and in vivo, and to profoundly reduce mammary tumor formation in mouse models. The RANKL inhibitor, denosumab, an FDA approved drug for the treatment of osteoporosis, is potentially an ideal chemopreventive agent for women with a germline BRCA1 mutation because it: (a) could potentially reduce breast cancer risk, and (b) concomitantly protect bone health in women who have already undergone bilateral salpingo-oophorectomy or in naturally postmenopausal women. The BRCA-P study will evaluate the reduction in the risk of any breast cancer (invasive or DCIS) in women with a germline BRCA1 mutation who are treated with denosumab compared to placebo. Sub-studies include measurement of bone turnover markers; epigenetic profiling of tumor tissues; measuring denosumab’s effect on bone and breast density; measurement of serum RANK, RANKL, OPG, progesterone, LH and FSH; and measurement of quality of life. Methods: This is a randomized, double-blind, placebo-controlled, multi-center international phase 3 study to determine the breast cancer risk reducing effect of denosumab in women carrying a germline BRCA1 mutation. Eligibility: Women with a confirmed BRCA1 germline mutation; ages ≥ 25 years and ≤ 55 years; no evidence of breast or ovarian cancer; no preventive breast surgery planned at randomization; ECOG performance status 0-1. Eligible participants will be randomized 1:1 to receive 120 mg of subcutaneous denosumab or placebo every 6 months for 5 years. Thereafter, all participants will be followed up for 5 years. Primary endpoints: Time to the occurrence of any breast cancer (invasive or DCIS). Secondary endpoints: Time to invasive triple negative breast cancer; time to other BRCA1 mutation associated malignancies, time to clinical fractures. Statistically, a 35% reduction in breast cancer risk would be detected with an 80% power and a two-sided significance level of 5% if 167 breast cancer cases are observed. We expect to observe the number of events needed if 1459 subjects per group (2918 in total) are randomized. The study is currently enrolling participants in Austria, Australia, Israel and Spain. The study will shortly begin accrual in Germany, United Kingdom, and at more than 30 sites across the United States. Globally, the trial is coordinated by the Austrian Breast &amp; Colorectal Cancer Study Group and by the Alliance for Clinical Trial in Oncology in the US. EudraCT: 2017-02505-35. Clinical trial information: NCT04711109.

Evaluation of bovine visual ELISA test for detection of pregnancy-associated glycoproteins in early pregnancy diagnosis in goats

Pregnancy diagnosis is the primary factor for improving reproductive performance and high economic efficiency in herds. Early pregnancy diagnosis, on the other hand, allows livestock to optimise production with greater reproductive performance and correct it with timely intervention. In the present study, it was aimed to investigate the effectiveness and reliability of the commercial rapid visual pregnancy test kit prepared for the detection of pregnancy-associated glycoproteins from blood serum in early pregnancy diagnosis in goats. Healthy and fertile, 3–5 years old 150 Damascus goats were used in the study. Oestrous synchronisation was applied to the goats between the anoestrous period and the onset of the transition period. Goats in oestrous were bred naturally. Blood samples were taken from the goats on the 28th day after their breeding. Progesterone measurement and rapid visual pregnancy test were performed from the blood samples taken. For the diagnosis of pregnancy, transabdominal ultrasonography was applied to the goats 50 days after the breeding. Ultrasonographic examination results were used as reference value. Sensitivity, specificity, positive predictive value, and negative predictive value ratios of serum progesterone measurement and visual PAG-ELISA kit were determined as 88.23%, 91.46%, 89.55%, 90.36% and 94.12%, 80.49%, 80%, 94.29%, respectively. In the study, it was ascertained that progesterone concentration results were in good agreement with ultrasonography results (kappa=0.798), and visual PAG-ELISA results were in good agreement with ultrasonography results (kappa = 0.735). Moreover, the concordance of progesterone concentration results with visual PAG-ELISA results was also found to be excellent (kappa = 0.828). The ability to accurately diagnose serum progesterone measurement and visual PAG-ELISA kit was found to be 90% and 86.67%, respectively. In conclusion, it can be accepted that the visual PAG-ELISA test in goats is useful in distinguishing pregnant from non-pregnant animals in the early stages of pregnancy. It can be said that in practice it can be used alone or in combination with other methods.

Impact of Serum Progesterone Levels on Pregnancy Outcomes in Patients Undergoing Artificial Endometrial Preparation for Embryo Transfer

In this retrospective cohort study, we examined the impact of measuring serum progesterone (P) levels on pregnancy outcomes in patients undergoing artificial endometrial preparation and embryo transfer (ET). We analyzed 342 ET cycles at the blastocyst stage, either from autologous or donated oocytes, in a private fertility care center. ET cycles were performed after an artificial endometrial preparation with a sequential administration of estradiol valerate followed by vaginal micronized progesterone. In the study population, when serum P levels were lower than 10.0 ng/ml the day prior to ET, a subcutaneous preparation of P was added, attempting to bring its levels to the luteal phase support. Interestingly, in the case of autologous ET, the rates of early pregnancy loss were reduced by measuring and eventually supplementing serum P levels. Keywords: Serum progesterone; Blastocyst transfer; Early pregnancy loss; Frozen embryo transfer; Endometrial preparation Abbreviations: P: Progesterone; ET: Embryo transfer; IVF: In vitro fertilization; HRT: Hormone replacement therapy; OPU: Oocyte pick-up; ICSI: Intracytoplasmatic sperm injection

Can endocrine characteristics of early pregnancy following natural cycle cryopreserved embryo transfer predict live birth?

Research questionCan serial measurements of serum oestradiol, progesterone and β-human chorionic gonadotrophin (HCG) concentrations, starting from the day of the first positive pregnancy test, predict live birth after natural cycle frozen-thawed embryo transfer (NC-FET)? DesignThis was a historical cohort study of women with a positive pregnancy test following NC-FET, between March 2009 and January 2020. Serum β-HCG, oestradiol and progesterone concentrations were measured on the day of the first pregnancy test and 48 and 96 h later. Pregnancies resulting in a live birth were compared with non-viable pregnancies. ResultsOf 101 women with a positive pregnancy test included in the study, 78 had a live birth and 23 had a non-viable pregnancy. Serum β-HCG concentrations were comparable on the day of the first pregnancy test (P = 0.09) but became significantly higher in women with a live birth 48 and 96 h later (P = 0.018 and P = 0.003). Serum oestradiol concentrations were higher in women with a live birth at all three measurements (P = 0.02, P = 0.007 and P = 0.02). Serum progesterone concentrations were higher 48 h after the first pregnancy test in women with a live birth (P = 0.04). On multivariate analysis, after controlling for the women's ages and number of embryos transferred, serum concentrations above the 25th percentile for oestradiol (>488–526 pmol/L) and progesterone (>63–70 nmol/L) were independent predictors of live birth at all three measurements. ConclusionsIncreased serum oestradiol and progesterone concentrations in early NC-FET pregnancies are associated with increased likelihood of live birth. Oestradiol and progesterone concentrations can be used in conjunction with β-HCG to predict pregnancy viability and assist in patient counselling.

Are serum progesterone measurements truly representative for the identification of an adequate luteal phase in hormonal replacement therapy frozen embryo transfers?

Progesterone (P4) is crucial for the achievement and maintenance of a pregnancy and with rising numbers of frozen embryo transfers (FETs) performed worldwide, the search for the 'optimal' P4 levels in HRT FET cycles became a focus of research. Certainly, measurement of systemic P4 levels is an easy applicable tool and P4 levels, considered as being too low, could be addressed by changing and/or increasing exogenously administered P4. However, the question must be raised whether the sole measurement of systemic P4 levels is reflective for the endometrial status and the endometrial receptivity in HRT FET cycles, since systemic P4 levels do not reflect the dynamic of the endometrial changes, deemed necessary to prepare the endometrium for implantation. Moreover, different types of P4 administration routes will exhibit distinct different patterns of P4 release, affecting the process of secretory transformation and last but not least, embryonic factors are almost fully neglected in this concept. This opinion article aims to raise critical points towards the 'sole' focus on systemic P4 levels in HRT FET cycles and raises the question whether 'serum P4 measurements are truly representative for the identification of an adequate luteal phase in HRT FETs'?.

Return to ovulation after Sayana Press is injected every 4 months for one year: Empirical and pharmacokinetic/pharmacodynamic modeling results

ObjectiveTo characterize return to ovulation after injecting Sayana Press (104 mg/0.65 mL medroxyprogesterone acetate [MPA] in the Uniject device) every 4 months for 1 year of treatment. Study designWe followed a subset of women for return to ovulation in a trial that demonstrated Sayana Press remains highly effective when the subcutaneous reinjection interval is extended from 3 to 4 months. We measured serum progesterone in weeks 38 to 42 and 46 to 50 after a final (third) injection and used a concentration ≥4.7 ng/mL as a surrogate for ovulation. We also performed pharmacokinetic and pharmacodynamic modeling to predict differences in MPA accumulation and return to ovulation had - contrary to fact - injections been given every 3 months. ResultsTen of 19 women (53%; 95% confidence interval: 29–76) ovulated within 50 weeks of their last injection. We predicted that typical 12-month trough MPA concentrations are 34% lower (0.46 vs 0.69 ng/mL) and the median time from last dose to ovulation is 1.1 months shorter (13.1 vs 14.2 months) when injections are given every four months for 1 year. ConclusionExtending the Sayana Press reinjection interval from 3 to 4 months leads to less drug accumulation, without a noticeable loss in efficacy. Although the Sayana Press patient leaflet specifies that over 80% of women desiring pregnancy will conceive within a year of stopping the method (independent of treatment duration), our empirical and modeling results indicate women should anticipate waiting a year or more for fertility to return after repeat dosing, with a somewhat shorter delay were the reinjection interval extended to four months. ImplicationsProviders should counsel women regarding the distinct possibility that return to fertility will take a year or longer following repeat use of Sayana Press. Extending the dosing interval from 3 to 4 months would result in approximately a 1-month shorter delay, without any appreciable reduction in contraceptive efficacy.

Early Serum Progesterone Measurement on 9th Day after Oocyte Retrieval can be used as a Predictor of Fresh Intracytoplasmic Sperm Injection Cycle Success

BACKGROUND: In intracytoplasmic sperm injection (ICSI) infertility treatment cycles, measuring serum Progesterone level at day 9 after oocyte retrieval could be used as a predictor of success. METHODS: Sixty-nine women were prospectively included in this study, treated with fresh embryo transfer ICSI cycles. Progesterone analyses were performed on the day of oocyte pick up (day 0) at serum and follicular fluid, then re-assessment at serum on day 9 after oocyte retrieval. The data were compared to evaluate the correlation among hormones measured on day 0 and day 9 with pregnancy rate. RESULTS: Pregnancy rate of Iraqi women was 22% (n = 15), mean serum progesterone on day 9 among pregnant ladies was (mean ± SD, 39.5 ± 13.0) which was significantly higher than that who failed to get pregnant (mean 23.2 ± 11, p = 0.001), then after adjustment of the baseline readings (day 0) estimated mean = 11.1. The differences were still significant, receiver operating characteristic curve area showed that serum Progesterone on day 9 after pick up can differentiate correctly between those who will conceive and those who will not, with a sensitivity = 0.933 and specificity = 0.519, at cut off point = 22.33 and above, (Area under the curve = 0.822, p = 0.001). CONCLUSION: Serum progesterone on day 9 could be one of the predictors of endometrial receptivity and pregnancy, which is actually of great value for both doctors and patients during that stressful period till the date of confirmation, which might negatively affect treatment outcome, as well as the psychosocial and pharmacological impact of medication and limited activity for a failed one.