Vaginal Progesterone For Luteal Support Research Articles

P-585 Vaginal progesterone associated with oral dydrogesterone versus vaginal progesterone for luteal support in letrozole-hcg cycles for thawed embryo transfer: a non-inferiority prospective cohort study

Abstract Study question Does micronized vaginal progesterone (MVP) associated with oral dydrogesterone (DYG) an alternative for luteal support in Letrozole-hcg cycles for thawed embryo transfer? Summary answer The association of MVP and DYG is a non-inferior alternative to only MVP for luteal support in thawed embryo transfer in Letrozole-hcg cycles. What is known already Endometrial preparation is essential for thawed embryo transfer. Several protocols involving different luteal support with progesterones are available. Moreover, the presence of corpus luteum decreases the obstetrical morbidity mainly linked to hypertensive disorders. Letrozole-hcg administration is a good alternative for frozen embryo transfer (FET). However, the literature lacks information about the comparison among the different protocols for luteal support in Letrozole-hcg cycles. Dydrogesterone is an oral progesterone with some unique characteristics which could be utilized with some advantage for luteal support, including oral administration and some immunological activity. Study design, size, duration This is a prospective non-inferiority cohort study performed at an infertility clinic including patients performing the first FET cycle during 2023. Reproductive outcomes were compared between patients receiving 600 mg (3x200 mg) of MPV or 40 mg of DYG plus 400 mg of MVP after Letrozole-hcg administration. Participants/materials, setting, methods All patients (aged 23-39 years) undergoing their first FET cycle during 2023 were included in this study (n = 169), divided into two groups: MVP+DYG (n = 54) or MVP (n = 115) for luteal support after Letrozole-hcg. Letrozole was administered for 5 days (2,5 mg/bid) and hcg was done when a dominant follicle reached 18 mm with a follicular endometrium measuring at least 7 mm. Main results and the role of chance Both groups were equivalent in terms of age, infertility aetiology, BMI and AMH (P > 0.05). Moreover, the proportion of cleavage or blastocyst stage was also similar between both groups (57% blastocyst transfer for MVP+DYG and 50% blastocyst transfer for MVP group, P > 0.05). The number of transferred embryos was (mean ±SD) 1.6±0.5 for both groups, P > 0.05. Furthermore, the number of top-quality embryos (cleavage stage or blastocyst) was also similar, P > 0.05. Moreover, clinical pregnancy (> 12 weeks) was 42% in MVP+DYG group versus 31% in the MVP group (-0.22-1.27, P = 0.156) and the early pregnancy loss per positive hcg test did not differ (18% for MVP+DGY and 22% for MVP, P = 0.687). In addition, we performed a multivariable analysis controlling possible confounders for clinical pregnancy: BMI, age, AMH, embryo quality, infertility aetiology and embryo stage during the transfer, and only age (0.86; 95%CI -0.229 to -0.064, P = 0.001) was related to clinical pregnancy. Limitations, reasons for caution The main limitation is the cohort design of our study, with an inherent risk of bias (selection bias). Moreover, we calculated this study to achieve the power for a non-inferiority comparison, not superiority comparison. Wider implications of the findings This is the first study comparing MVP+DYG to only MVP in patients submitted to FET using the Letrozole-hcg protocol. We demonstrated in this non-inferiority study the usefulness of adding DYG. Moreover, our results were promising showing a trend towards better pregnancy rates after MVP+DYG. Trial registration number not applicable

Luteal phase support with progesterone does not improve pregnancy rates in patients undergoing ovarian stimulation with letrozole

Research questionDoes luteal phase support with vaginal progesterone improve clinical pregnancy rates in patients undergoing ovarian stimulation with letrozole? DesignThis was a retrospective cohort study of patients undergoing ovarian stimulation with letrozole paired with intrauterine insemination (IUI) or timed intercourse (TIC) from January 2018 to October 2021. The primary outcome of clinical pregnancy rate (CPR) was calculated for cycles with and without luteal phase progesterone support. Univariate logistic regressions were done to evaluate predictor variables for CPR. Clinically important covariates including age, body mass index, anti-Müllerian hormone concentration, diagnosis of ovulatory dysfunction and multifollicular development were included in a multivariate analysis evaluating the relationship between luteal progesterone use and odds of clinical pregnancy. Secondary outcomes including spontaneous abortion, biochemical pregnancy and ectopic pregnancy were calculated. Live birth rates were calculated for cycles in a secondary analysis. ResultsA total of 492 letrozole ovarian stimulation cycles in 273 patients were included. Of these cycles, 387 (78.7%) used vaginal progesterone for luteal support and 105 (21.3%) did not. The unadjusted CPR per cycle was 11.6% (45/387) with progesterone and 13.3% (14/105) without progesterone (P = 0.645). After adjusting for significant covariates including age, BMI, diagnosis of ovulatory dysfunction and multifollicular development, the odds for clinical pregnancy were not significantly improved in cycles with exogenous progesterone (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.48–2.75, P = 0.762). A follow-up analysis demonstrated that live birth rate was 10.7% (41/384) with and 12.5% (13/104) without luteal progesterone, respectively (P = 0.599). ConclusionsLuteal support with vaginal progesterone does not significantly improve CPR in ovarian stimulation cycles using letrozole.

P-116 Clinical predictors of live birth rate (LBR) in donor-intrauterine insemination (D-IUI) cycles

Abstract Study question Which clinical parameters can predict LBR in D-IUI cycles? Summary answer Only age returned as a clinical predictor of D-IUI LBR. Total motile sperm count for insemination (TMSC) and stimulation protocol may help clinicians optimise LBR. What is known already D-IUI cycles are a popular treatment option for patients requiring male gamete donation. For both patient and clinician, identification of parameters that can guide clinical decision-making during fertility treatment is important to optimise clinical outcomes. To date, few studies have investigated D-IUI cycle parameters with live birth as the primary outcome. Moreover, previous studies can be limited from lack of control of covariates, as well not accounting for data skewing from inclusion of multiple cycles per patient. Study design, size, duration A retrospective analysis of 1925 D-IUI cycles in 638 patients between 2018-2020 at a single UK-based centre was performed. All donors were recruited by the London Sperm Bank as per the HFEA regulations. Inclusion criteria for donor sperm quality were all samples that met the WHO criteria. Exclusion criteria were cycles where live birth outcome was unknown. Participants/materials, setting, methods Patients underwent natural or stimulation cycle. Stimulation included clomiphene or letrozole, gonadotrophins +/- GnRH agonist, an hCG trigger or LH-monitoring to time insemination and micronised vaginal progesterone for luteal support. Insemination was scheduled 24 hours following surge detection/trigger administration. TMSC is presented per 0.5ml vial, which is post-preparation sample for insemination. T-test for continuous variables and Fisher’s Exact test for categorical variables were performed. For multivariate analysis, a generalised mixed effects logistic regression was performed. Main results and the role of chance Median cohort age was 36 ± SE 0.1, median TMSC was 14x106 ± SE 0.2x106. Of recipients, 53% were same sex couples, 41% were single women, 6.3% were heterosexual couples. There was no significant difference in TMSCs between cycles that produced a live birth and those that did not (14x106 and 13.9x106 respectively, P = 0.1). Dividing TMSC into 5x106 increments demonstrated that small increases in LBR per cycle occurred between 2.5-25x106. On average, LBR increased by 1.3% with each increment up to 25x106, reaching 15%. Beyond this, no further increase in LBR was observed. However, these incremental increases were not statistically significant (P = 0.6). Gonadotrophin stimulation (without agonist) achieved significantly higher LBRs than all other protocols (17.1%, P < 0.001). This persisted when stratifying by age (<35; 30%, 35-37; 29%, 38+; 12.6%). A mixed effects logistic regression model demonstrated that only age returned as a significant negative predictor of LBR (aOR 0.9, 95% CI 0.86-0.94, P < 0.001). There was no effect of TMSC on LBR (aOR 1.0, 95% CI 0.99-1.02, P = 0.7). Gonadotropin stimulation was associated with over double increased odds of achieving a live birth, which came close to significance (aOR 2.29, 95% CI 0.98-5.4, P = 0.06). Limitations, reasons for caution The choice of management regimen could have been influenced by uncontrolled factors, introducing bias in this retrospective study. Other semen parameters were not included in the multivariate analyses which could, in turn, have affected live birth outcome, which should be considered. Wider implications of the findings These findings demonstrate that increasing TMSC may be associated with small rises in LBR up to 25x106 in D-IUI cycles. While gonadotrophin stimulation appeared most effective, only age was shown to be an independent predictor of LBR. Collectively, these parameters may assist clinicians in optimising LBR in D-IUI cycles. Trial registration number None

A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization.

STUDY QUESTION Is oral dydrogesterone 30 mg daily (10 mg three times daily [TID]) non-inferior to micronized vaginal progesterone (MVP) 600 mg daily (200 mg TID) for luteal support in in vitro fertilization (IVF), assessed by the presence of fetal heartbeats determined by transvaginal ultrasound at 12 weeks of gestation? SUMMARY ANSWER Non-inferiority of oral dydrogesterone versus MVP was demonstrated at 12 weeks of gestation, with a difference in pregnancy rate and an associated confidence interval (CI) that were both within the non-inferiority margin. WHAT IS KNOWN ALREADY MVP is routinely used in most clinics for luteal support in IVF, but it is associated with side effects, such as vaginal irritation and discharge, as well as poor patient acceptance. Dydrogesterone may be an alternative treatment due to its patient-friendly oral administration. STUDY DESIGN, SIZE, DURATION Lotus I was an international Phase III randomized controlled trial, performed across 38 sites, from August 2013 to March 2016. Subjects were premenopausal women (>18 to <42 years of age; body mass index (BMI) ≥18 to ≤30 kg/m2) with a documented history of infertility who were planning to undergo IVF. A centralized electronic system was used for randomization, and the study investigators, sponsor's study team, and subjects remained blinded throughout the study. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 1031 subjects were randomized to receive either oral dydrogesterone (n = 520) or MVP (n = 511). Luteal support was started on the day of oocyte retrieval and continued until 12 weeks of gestation (Week 10), if a positive pregnancy test was obtained at 2 weeks after embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE In the full analysis set (FAS), 497 and 477 subjects in the oral dydrogesterone and MVP groups, respectively, had an embryo transfer. Non-inferiority of oral dydrogesterone was demonstrated, with pregnancy rates at 12 weeks of gestation of 37.6% and 33.1% in the oral dydrogesterone and MVP treatment groups, respectively (difference 4.7%; 95% CI: -1.2-10.6%). Live birth rates of 34.6% (172 mothers with 213 newborns) and 29.8% (142 mothers with 158 newborns) were obtained in the dydrogesterone and MVP groups, respectively (difference 4.9%; 95% CI: -0.8-10.7%). Oral dydrogesterone was well tolerated and had a similar safety profile to MVP. LIMITATIONS, REASONS FOR CAUTION The analysis of the results was powered to consider the clinical pregnancy rate, but the live birth rate may be of greater clinical interest. Conclusions relating to the differences between treatments in live birth rate, observed in this study, should therefore be made with caution. WIDER IMPLICATIONS OF THE FINDINGS Oral dydrogesterone may replace MVP as the standard of care for luteal phase support in IVF, owing to the oral route being more patient-friendly than intravaginal administration, as well as it being a well tolerated and efficacious treatment. STUDY FUNDING/COMPETING INTEREST(S) Sponsored and supported by Abbott Established Pharmaceuticals Division. H.T.'s institution has received grants from Merck, MSD, Goodlife, Cook, Roche, Besins, Ferring and Mithra (now Allergan) and H.T. has received consultancy fees from Finox, Ferring, Abbott, ObsEva and Ovascience. G.S. has nothing to disclose. E.K. is an employee of Abbott GmbH. G.G. has received investigator fees from Abbott during the conduct of the study; outside of this submitted work, G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, Glycotope, as well as personal fees from VitroLife, NMC Healthcare LLC, ReprodWissen LLC and ZIVA LLC. TRIAL REGISTRATION NUMBER NCT01850030 (clinicaltrials.gov). TRIAL REGISTRATION DATE 19 April 2013. DATE OF FIRST PATIENT'S ENROLLMENT 23 August 2013.

Lotus I: Рандомизированное III фазы контролируемое исследование сравнения пероральной формы дидрогестерона и вагинальной формы микронизированного прогестерона для поддержки лютеиновой фазы в циклах экстракорпорального оплодотворения, фокус на субанализ ро

Lotus I: Рандомизированное III фазы контролируемое исследование сравнения пероральной формы дидрогестерона и вагинальной формы микронизированного прогестерона для поддержки лютеиновой фазы в циклах экстракорпорального оплодотворения, фокус на субанализ ро

Combined progesterone (IM + V) versus vaginal progesterone for luteal support in cleavage-stage embryo transfer cycles of good prognosis patients

Many reports led to the consensus on the use of progesterone (P) for luteal-phase support. Vaginal P application is the method of choice due to its simplicity and high patient convenience but is hampered by application difficulties and personal or cultural aversions. Inappropriate vaginal P use may alter successful implantation, leading physicians to consider alternate P application routes. A worldwide survey revealed that intramuscular plus vaginal P (combined P) is the method used in nearly one-third of in vitro fertilization (IVF) cycles, particularly in Asia and North America; unfortunately, the outcomes of this approach have not been clearly elucidated. In the current analysis, we evaluated any additional benefit of short course parenteral P in addition to vaginal P capsules during a specific period in terms of implantation, pregnancy rates, miscarriages and ectopic pregnancies in cleavage stage embryo transfer (ET) cycles of good-prognosis patients. Despite significantly higher implantation rates in the combined arm, clinical and ongoing pregnancies were comparable in both groups, whereas a trend toward increased pregnancy rates was observed with combined support. The available data are too limited to draw conclusions.

Comparison of the efficacy and tolerability of two formulations of vaginal progesterone for luteal phase support in frozen embryo transfer cycles

Comparison of the efficacy and tolerability of two formulations of vaginal progesterone for luteal phase support in frozen embryo transfer cycles

Analysis of the bleeding pattern in assisted reproduction cycles with luteal phase supplementation using vaginal micronized progesterone

This study was designed to determine the effects of a vaginal micronized progesterone preparation on bleeding patterns and pregnancy outcomes after in-vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI). The study population consisted of 149 consecutive women who had undergone IVF-ICSI using 'long-protocol' stimulation with buserelin-human menopausal gonadotrophin (HMG). A retrospective chart analysis of computerized medical records was undertaken. Vaginal progesterone (200 mg three times daily) was begun the day before oocyte retrieval and continued for a minimum of 16-19 days following human chorionic gonadotrophin (HCG) administration. Occurrence of bleeding following HCG injection, pregnancy rate and outcomes, and serum concentrations of oestradiol were measured. Women undergoing IVF and embryo transfer with ICSI and using vaginal progesterone for luteal support had normal luteal phase lengths (day of HCG minus day of onset of bleeding). In the absence of pregnancy, bleeding occurred after 19.2 +/- 3.9 days (mean +/- SD). Out of the pregnant group only three women bled within 19 days of HCG administration: two had biochemical pregnancies which spontaneously vanished and one evolved to term. The results reflect the normal bleeding pattern to be expected when vaginal progesterone is used for luteal support in IVF and embryo transfer, an approach whose efficacy has been amply proven. No shortened luteal phases were observed using vaginally administered progesterone.