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Background There is limited literature investigating the effects of body mass index (BMI) and androgen level on in vitro fertilization (IVF) outcomes with a gonadotropin-releasing hormone (GnRH)-antagonist protocol in polycystic ovary syndrome (PCOS). Androgen-related variation in the effect of body mass index (BMI) on IVF outcomes remains unknown. Methods In this retrospective study, 583 infertile women with PCOS who underwent IVF using the conventional GnRH-antagonist protocol were included. Patients were divided into four groups according to BMI and androgen level: overweight- hyperandrogenism(HA) group, n = 96, overweight-non-HA group, n = 117, non-overweight-HA group, n = 152, and non-overweight-non-HA group, n = 218. Results A significantly higher number of oocytes were retrieved, and the total Gn consumption as well Gn consumption per day was significantly lower, in the non-overweight groups than in the overweight groups. The number of available embryos was significantly higher in the HA groups than in the non-HA groups. Clinical pregnancy rate was of no significant difference among four groups. Live-birth rates in the overweight groups were significantly lower than those in non-overweight-non-HA group (23.9, 28.4% vs. 42.5%, P

This study investigates the predictive power of serum progesterone/estradiol (P/E2) level for estimating the live birth rate in patients who had a serum progesterone (P) rate ≥ 1.5 ng/mL on the human chorionic gonadotropin (hCG) administration day and who received the gonadotropin-releasing hormone (GnRH) antagonist protocol and intracytoplasmic sperm injection (ICSI). This retrospective cohort study included 176 cycles. The P/E2 ratio was lower in patients with a live birth (0.73 ± 0.54) than those without a live birth (1.05 ± 1.38), but the difference was not statistically significant (p = .158). According to the receiver operating characteristic curve analysis of the hCG day P/E2 ratio, the area under the curve was 0.579 (95% confidence interval: 0.478 - 0.680, p = .158) for predicting live birth. In conclusion, this study suggests that a P/E2 ratio is not a significant predictor of a live birth rate in the patients with an hCG-day serum progesterone level of ≥1.5 ng/mL undergoing GnRH antagonist ICSI cycles with a fresh embryo transfer. Impact statement What is already known on this subject? As the progesterone (P) levels in the late follicular phase correlate with the estradiol (E2) levels and the increase in mature follicles, earlier studies have proposed the trigger-day progesterone/estradiol (P/E2) ratio as a potential new marker for a premature luteinisation and live birth success. Most of these studies were conducted on long agonist cycles, and found that arbitrarily defined P/E2 ratio of >1 to be associated with poor pregnancy outcomes. What do the results of this study add? This study retrospectively examines the gonadotropin-releasing hormone (GnRH) antagonist cycles with a trigger-day serum P value of ≥1.5 ng/mL undergoing the intracytoplasmic sperm injection (ICSI) treatment. The receiver operating characteristic (ROC) curve analysis did not identify a statistically significant threshold value for the trigger-day P/E2 ratio that was beneficial in predicting a live birth. The P/E2 ratio was also lower in the cycles with a live birth than those without a live birth, although the difference was not statistically significant. What are the implications of these findings for clinical practice and/or further research? The trigger-day P/E2 ratio does not seem to be an efficient prognostic factor for a live birth in the GnRH antagonist ICSI cycles with a trigger-day serum progesterone level of ≥1.5 ng/mL. Further studies are needed to clarify the association of the trigger-day P/E2 ratio and the pregnancy outcomes in GnRH antagonist ICSI cycles.

A AkAr, Yavuz Emre/0000-0003-0815-3522; Ozmen, Batuhan/0000-0002-4504-669X; Atabekoglu, Cem Somer/0000-0003-0264-0709; Berker, Bulent/0000-0001-7346-7128; Sonmezer, Murat/0000-0001-6101-1414; ates, can/0000-0003-2286-4398 WOS: 000443619200004 PubMed: 30202623 Objective: To investigate the impact of peri-implantation prednisolone use and its duration in antagonist co-treated assisted reproductive technology (ART) cycles of patients with good prognosis. Materials and Methods: Infertile patients treated with gonadotropin-releasing hormone antagonist protocol between January 2010 and June 2013 were included. The patients in group A (n=196) received no prednisolone. The patients in groups B (n=397) and C (n=371) received 5 mg oral prednisolone daily, for 4 and 12 days following embryo transfer, respectively. The main outcome parameter was live birth rate. Results: The ages of the groups were 30.1 +/- 4.6, 31.5 +/- 4.5, and 30.9 +/- 4.7 years, respectively (p=0.163). There was no statistically significant difference between the groups regarding cycle characteristics. Implantation rates were 20.7%, 24.6%, and 23.8%, respectively (p=0.163). Miscarriage rates were 1.5%, 3.5%, and 3.2%, respectively (p=0.859). Live birth rates were 28.7%, 29.3%, and 32.8%, respectively (p=0.482). Conclusion: Empiric prednisolone administration during the peri-implantation period does not seem to have beneficial effects in ART cycles of patients with good prognosis.

Background The prevalence of infertility among Chinese women of reproductive age was estimated to be 25.0%. Currently, assisted reproductive technology, such as in vitro fertilization (IVF), is considered the most effective treatment for infertility. Cetrorelix is a subcutaneously administered gonadotropin-releasing hormone antagonist approved for clinical use in IVF therapy. To improve IVF outcomes, there is a need to identify predictive markers of successful clinical pregnancy with gonadotropin-releasing hormone antagonists.Methods The retrospective FASSION study assessed clinical outcomes and factors associated with clinical pregnancy rates of Chinese patients undergoing fertility treatment with cetrorelix and IVF/intracytoplasmic sperm injection (ICSI) cycles. We analyzed medical records of infertile women aged ≤35 years, with baseline serum follicle-stimulating hormone level ≤10 mIU/mL, body mass index ≤30 kg/m2 and normal uterine cavity, who underwent IVF/ICSI cycles using cetrorelix at four centers in China. The primary objective was identifying factors associated with clinical pregnancy rates by validating a predictive model for clinical outcome evaluation. Secondary objectives were clinical outcomes and safety.Results In total, 2972 women were included. After adjusting for confounders, on the day of human chorionic gonadotropin triggering, an increased endometrial thickness was associated with a higher probability of pregnancy outcome (p=0.0001) and a higher progesterone level was associated with a lower probability of pregnancy outcome after fresh embryo transfer (ET) per initiated cycle (p=0.0256). Per ET cycle, the ongoing pregnancy and clinical pregnancy rates were 45.2% and 53.0%, respectively, with an implantation rate of 37.3% per ET. The early miscarriage and cycle cancellation rates were 13.4% and 5.7%, respectively. A total of 970 live births were reported. The live birth rate per initiated cycle was 32.6% and that per ET cycle was 45.2%. Fifty-one patients (1.7%) reported an ovarian hyperstimulation syndrome event, with severe events in 17 (0.6%) patients.Conclusions This prediction model may be useful for the preliminary screening of IVF patients and help improve clinical pregnancy outcomes.

Background: Luteal support is a key to patients undergoing in vitro fertilization and embryo transfer (IVF-ET) with gonadotropin-releasing hormone (GnRH)-antagonist protocol. This study aimed to compare the effect between vaginal progesterone (VP) and intramuscular progesterone (IMP) with GnRH-antagonist protocol after IVF-ET. Methods: A total of 1760 patients (18 years ≤ age ≤35 years) undergoing IVF-ET with GnRH-antagonist protocol were studied retrospectively between September 2014 and August 2015 in Peking University Third Hospital. In the patients, 1341 patients received VP (VP group) and 419 patients received IMP (IMP group) as luteal support. We compared clinical outcomes between these two groups. The primary objective of the study was the live birth rate. Measurement data between the two groups were conducted using independent samples t-test. The variables in line with non-normal distribution were expressed as median (p25 and p75) and were compared using nonparametric Mann–Whitney U-test. Results: Live birth rate in VP group was 38.55%, significantly higher than that in the IMP group, which was 30.79% (χ2 = 8.287, P = 0.004). The clinical intrauterine pregnancy rate and implantation rate in VP group were also significantly higher than those in the IMP group (clinical intrauterine pregnancy rate 47.35% vs. 41.29%, χ2 = 4.727, P = 0.030; implantation rate 30.99% vs. 25.26%, χ2 = 14.546, P < 0.001). Any statistically significant differences in ectopic pregnancy and abortion rates between two groups were not observed. Conclusion: Luteal support with VP had better clinical outcomes for young women undergoing IVF-ET with GnRH-antagonist protocol. Key words: Gonadotropin-Releasing Hormone Antagonist; Intramuscular Progesterone; Undergoing In vitro Fertilization and Embryo Transfer; Vaginal Progesterone

PURPOSE OF REVIEW: Traditional approach of ovarian stimulation monitoring for in-vitro fertilization involves transvaginal sonography and serum estradiol measurements. Accumulating evidence has shown that hormonal evaluations during ovarian stimulation allow individual cycle optimization, moving away from only predicting the risk of ovarian hyperstimulation syndrome, but in addition assessing the impact of ovarian stimulation on endometrial receptivity, quality of oocytes, and subsequently embryos. The purpose of this review is to discuss the relevance and added value of hormonal monitoring during ovarian stimulation in gonadotropin-releasing hormone antagonist cycles where most of the advances have occurred. RECENT FINDINGS: Basal hormonal status, particularly estradiol, progesterone, and luteinizing hormone are instrumental in prediction of the patients with poor prognosis. Estradiol levels on the day of trigger are less sensitive in predicting ovarian hyperstimulation syndrome then the number of folliclesmore than 11 mm in diameter. Progesterone elevation on the day of trigger is associated with lower pregnancy rates. The gold standard treatment for progesterone elevation is to adopt a freeze-all strategy when the threshold of 1.50 ng/ml is exceeded. The effect of progesterone elevation on embryo quality remains to be confirmed by more trials. SUMMARY: Endocrine monitoring during ovarian stimulation allows fine-tuning of the physiology of the stimulated cycle and thereby increases the chances of successful treatment outcome.

Objective To explore factors causing a premature rise in luteinizing hormone among high ovarian responders undergoing the gonadotropin-releasing hormone (GnRH) antagonist ovarian stimulation protocol. Methods The present retrospective study included healthy women undergoing fresh cycles using a fixed GnRH antagonist protocol with a predicted high response and antral follicle count (AFC) of at least 15 at the Reproductive Medicine Center of Tongji Hospital, China, between January 1 and December 31, 2016. Treatment-related characteristics, hormone changes, and pregnancy outcomes were compared between patients who did or did not experience a premature luteinizing hormone rise. Results There were 314 patients included; 49 experienced premature luteinizing hormone increases. Among patients who experienced a premature rise in luteinizing hormone, a lower two pronuclear embryo rate (P=0.038); fewer high-quality embryos (P=0.020); higher serum luteinizing hormone (P=0.006), progesterone (P=0.013), and estradiol (E2) levels (P=0.003) on the day of human chorionic gonadotropin administration; a lower clinical pregnancy rate (P=0.031); and a higher cancellation rate (P=0.006) were observed. AFC of at least 22 (P=0.001) and E2 of 669 pg/mL or higher at the start of GnRH antagonist administration were predictive of early (P=0.036) and late (P=0.033) premature luteinizing hormone increases. Conclusion Earlier administration of GnRH antagonist could avoid premature luteinizing hormone increases among high ovarian responders, especially those with a starting AFC of 22 or more.

Objective To determine the optimal criteria at which to start GnRH antagonists during controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Design Retrospective clinical cohort. Setting IVF clinics. Patient(s) Women undergoing fresh autologous IVF using GnRH antagonist for ovulation suppression during COH. Intervention(s) Measurement of lead follicle size, E2 level, and cycle day of stimulation on day of antagonist initiation. Main Outcome Measure(s) Clinical pregnancy rate (PR). Result(s) The highest clinical PR was achieved when the antagonist was started when a lead follicle reached 14–15.9 mm in size (mean clinical PR 21.3; 95% confidence interval [CI] 19.3, 23.6) on cycle day 6 (mean clinical PR 22.2; 95% CI 17, 28.4), or when the E2 level was between 500 and 599 pg/mL (mean clinical PR 25.4; 95% CI 19.5, 32.4). Starting antagonists when the E2 level was 1,100 pg/mL reduced the odds of clinical pregnancy by 40% (odds ratio 0.60, 95% CI 0.5, 0.7). Conclusion(s) Cycle day, E2 level, and follicle size at time of antagonist start are all independent predictors of a clinical pregnancy after IVF. Initiating antagonists when the E2 level is extremely low ( 1,100 pg/mL) significantly reduces the odds of pregnancy.

Background: The use of embryo cryopreservation excludes the possible detrimental effects of ovarian stimulation on the endometrium, and higher reproductive outcomes following this policy have been reported. Moreover, gonadotropin-releasing hormone agonist trigger in gonadotropin-releasing hormone (GnRH) antagonist cycles as a substitute for standard human chorionic gonadotropin trigger, minimizes the risk of ovarian hyperstimulation syndrome (OHSS) in fresh as well as frozen embryo transfer cycles (FET).Objective: To compare the reproductive outcomes and risk of OHSS in fresh vs frozen embryo transfer in high responder patients, undergoing in vitro fertilization triggered with a bolus of GnRH agonist.Materials and Methods: In this randomized, multi-centre study, 121 women undergoing FET and 119 women undergoing fresh ET were investigated as regards clinical pregnancy as the primary outcome and the chemical pregnancy, live birth, OHSS development, and perinatal data as secondary outcomes.Results: There were no significant differences between FET and fresh groups regarding chemical (46.4% vs. 40.2%, p=0.352), clinical (35.8% vs. 38.3%, p=0.699), and ongoing (30.3% vs. 32.7%, p=0.700) pregnancy rates, also live birth (30.3% vs. 29.9%, p=0.953), perinatal outcomes, and OHSS development (35.6% vs. 42.9%, p=0.337). No woman developed severe OHSS and no one required admission to hospital.Conclusion: Our findings suggest that GnRHa trigger followed by fresh transfer with modified luteal phase support in terms of a small human chorionic gonadotropin bolus is a good strategy to secure good live birth rates and a low risk of clinically relevant OHSS development in in vitro fertilization patients at risk of OHSS.

Objective To evaluate COS and oocyte retrieval results in ART treatment cycles initiated at any stage of the menstrual cycle (random start) in cancer patients, who could not postpone the onset of cancer treatment. Methods Prospective observational study of 26 women with cancer, with an indication to start cancer treatment within the next 20 days and wishing to preserve their fertility. Ovarian stimulation started immediately with FSH followed by GnRH antagonist for pituitary suppression and GnRH agonist for oocyte maturation. Treatment started from day 1 to day 14 of the menstrual cycle was considered to be in the follicular phase, and that started from day 15 to day 28 was considered to be in the luteal phase. Oocyte retrieval was performed 34 h after GnRH agonist administration. After identification and maturity classification, metaphase II oocytes were cryopreserved using vitrification. Results A total of 13 women had breast cancer, 4 ovarian cancer, 3 Central Nervous System cancer, 3 endometrial cancer, 2 cervical cancer and one bowel cancer. Thirteen patients started treatment during follicular phase and 13 during luteal phase. We found similar results for the duration of treatment, total dose of follicle stimulating hormone, number of ampoules of gonadotropin releasing hormone antagonist, mean number of follicles identified at ultrasound on the day of trigger and retrieval, number of aspirated oocytes and Metaphase II oocytes. Conclusion Random-start controlled ovarian stimulation for emergency fertility preservation for minimizing delay in oncologic treatment for cancer patients does not interfere with the number of metaphase II oocytes, and therefore can be routinely used for stimulation followed by cryopreservation.

Objective We investigated whether luteal estrogen administration and an early follicular Gonadotropin-releasing hormone antagonist (E/G-ant) priming protocol improves clinical outcomes in poor responders to controlled ovarian stimulation for in vitro fertilization (IVF)-embryo transfer, and identified underlying mechanisms. Methods This restrospective study consisted of 65 poor responders who underwent the E/G-ant priming protocol. Sixty-four other poor responders undergoing conventional protocols without pretreatment were included as the control group. Clinical outcomes were compared between 2 groups. Results The E/G-ant priming protocol group exhibited improvements over the control group in terms of the number of retrieved oocytes (3.58±2.24 vs. 1.70±1.45; P=0.000), mature oocytes (2.68±2.11 vs. 1.65±1.23; P=0.000), fertilized oocytes (2.25± 1.74 vs. 1.32±1.26; P=0.001), good embryos (1.62±0.91 vs. 1.14±0.90, P=0.021). Day 3 follicle-stimulating hormone (FSH; 8.40±4.84 vs. 16.39±13.56; P=0.000) and pre-ovulation progesterone levels (0.67 vs. 1.28 ng/mL; P=0.016) were significantly higher in the control group than in the E/G-ant priming group. The overall rate of positive human chorionic gonadotropin tests was higher in the E/G-ant priming group than in the control group (32.3% vs.16.1%; P=0.039). Also, clinical pregnancy rate (26.2% vs. 12.5%; P=0.048) and the rate of live births (23.1% vs. 7.1%; P=0.023) were significantly higher in the E/G-ant priming group than in the control group. Conclusion The E/G-ant priming protocol would lead to promising results in poor responders to IVF by suppressing endogenous FSH and by preventing premature luteinization.

The impact of exogenous luteinizing hormone (LH) supplementation to patients undergoing controlled ovarian stimulation with gonadotropin-releasing hormone (GnRH) antagonists on cycle outcomes is controversial. Here, we present a retrospective cohort study including cycles from December 2015 to December 2016. Totally 320 cycles were divided into two groups according to with or without exogenous LH supplementation. No significant differences regarding the number of retrieved oocytes, the number of good-quality embryos, and clinical pregnancy rate between the two groups were found. The logistic regression analysis revealed that LH supplementation was not independently associated with clinical pregnancy rate (OR = 0.577, 95% CI: 0.272-1.222, p = .58) or a biochemical pregnancy rate (OR = 0.922, 95% CI: 0.444-1.916, p = .83). When patients were divided into subgroups based on age, more retrieved oocytes (5.60 vs. 3.97, p = .04) and good-quality embryos (3.07 vs. 1.93, p = .01) were achieved in cycles with exogenous LH supplementation for 40 years and over group. We conclude that for aged women (40 years old and over), LH supplementation has a positive impact on the number of retrieved oocytes and good-quality embryos in GnRH antagonist cycles.

Objective: The aim of this study was to compare the effect of corifollitropin alfa (CFA) and recombinant follicle-stimulating hormone (rFSH) in poor-responder patients undergoing antagonist cycles. Materials and Methods: The study was a retrospective analysis of the treatment results of 214 poor responder patients who had been admitted to the In Vitro Fertilization Unit of İzmir Medical Park Hospital between November 2014 and November 2016. Intracytoplasmic sperm injections were performed in 38 patients (group 1) with CFA, and the remaining 176 (group 2) with rFSH for controlled ovarian hyperstimulation. Results: The age, body mass index, anti-müllerian hormone level, duration of infertility, duration of induction and antral follicle number were similar in the two groups. There was no difference in the total aspirated oocyte counts, mature oocyte ratio, fertilization rate, implantation rate, and clinical pregnancy rates between the two groups. The implantation rate was 9/38 (23.6%) in group 1 and 42/176 (23.8%) in group 2, whereas the clinical pregnancy rates were 16.3% and 17.2%, respectively. Conclusion: No difference was found in terms of oocyte count, fertilization rate, implantation rate, and clinical pregnancy rates of CFA or rFSH use in the antagonist cycles in poor-responder patients. © 2017 by Turkish Society of Obstetrics and Gynecology.

Introduction Scheduling of ovum pickup only on weekdays may result in cases of apparently suboptimal timing for human chorionic gonadotropin and ovum pickup. This study aimed to assess whether live-birth rates were reduced in women with a potentially suboptimal day for human chorionic gonadotropin and ovum pickup to avoid weekend work, according to ultrasonographic data on the day of human chorionic gonadotropin planning. Material and methods An evaluation of the optimal human chorionic gonadotropin priming date was performed in treatment protocols of 1000 consecutive patients undergoing their first in vitro fertilization/intracytoplasmatic sperm injection with single-embryo transfer. An ideal ovum pickup day was characterized by human chorionic gonadotropin-scheduling when three or more follicles reached 17 mm (day 0) or with one day of delay (day +1) (n = 760). A non-ideal ovum pickup was either early (day −1, −2, −3) (n = 24) or delayed (day +2, +3, +4) (n = 216). Live-birth rates in the ideal and non-ideal ovum pickup groups was set as primary outcome measure. Results Early-ovum pickups were excluded as they were infrequent. No differences between ideal and delayed ovum pickup groups were found regarding number of oocytes retrieved (9.87 vs. 9.78, p = 0.990), pregnancy rates (28.3% vs. 29.6%, p = 0.701) or live-birth rates (26.2% vs. 25.9%, p = 0.939). However, sub analyses indicated that treatment with gonadotropin releasing hormone antagonists resulted in significantly lower clinical pregnancy rates in delayed ovum pickups (odds ratio 0.46, p = 0.014), compared with agonist treatments. Conclusions Weekend work may not be needed for in vitro fertilization/intracytoplasmatic sperm injection- single-embryo transfer treatments. However, in gonadotropin releasing hormone antagonist cycles, delaying ovum pickup more than one day may result in unfavorable outcomes.

The purpose of this paper is to assimilate all data pertaining to the use of gonadotropin-releasing hormone (GnRH) antagonists in in vitro fertilization cycles after ovulation trigger to reduce the symptoms of ovarian hyperstimulation syndrome (OHSS). A systematic review of the literature was performed to identify all studies performed on the use of a GnRH antagonist in IVF cycle post-ovulation trigger with patients at high risk for OHSS. Ten studies were identified and reviewed. Descriptions of the studies and their individual results are presented in the following manuscript. Due to significant heterogeneity among the studies, it was not possible to perform a group analysis. The use of GnRH antagonists post-ovulation trigger for treatment of OHSS has been considered for almost 20 years, though research into its use is sparse. Definitive conclusions and recommendations cannot be made at this time, though preliminary data from these trials demonstrate the potential for GnRH antagonists to play a role in the treatment of OHSS in certain patient populations.

STUDY QUESTION Does the time from ovum pick-up (OPU) to frozen embryo transfer (FET) affect reproductive outcomes in a freeze-all strategy? SUMMARY ANSWER Our study did not detect statistically significant differences between first and subsequent cycles, clinically relevant differences are not ruled out and further and larger studies are required. WHAT IS KNOWN ALREADY Following controlled ovarian hyperstimulation (COH) delaying FET until the endometrium has returned to an optimal pre-stimulation state may have a significant emotional impact on patients, which adds to the stress and anxiety accompanying a standard IVF cycle. Currently there is no agreement on the best time to perform a FET after a freeze-all cycle in order to maximize reproductive outcomes for the patient. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of 512 freeze-all cycles, performed between January 2012 and December 2014. COH was performed by either a GnRH antagonist (n = 397) or a long GnRH agonist protocol (n = 115). Ovulation was triggered using either a GnRH agonist (n = 258) or hCG (n = 254). Endometrial preparation was performed in an artificial cycle by either oral (n = 238) or transdermal (n = 274) oestrogen. Differences were considered significant if P < 0.05. PARTICIPANTS/MATERIALS, SETTING, METHODS Reproductive outcomes between FETs which took place either within the first menstrual cycle following OPU (Cycle 1; n = 263) or afterwards (Cycle ≥2; n = 249) were compared. Student's t-test for independent samples, Mann-Whitney U-test and Chi-square analysis were used where appropriate. A multivariable logistic regression analysis was performed adjusting for maternal age, drug used for ovulation trigger, number of retrieved oocytes, number of embryos obtained, day of embryonic development at transfer, number of embryos transferred and type of endometrial preparation. Differences were considered significant if P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE Live birth rate (LBR) was significantly higher in FET performed during Cycle 1 vs Cycle ≥2 (37.6% vs 27.3%, respectively; P = 0.01) before adjusting for confounding factors. We found no difference for biochemical pregnancy (49.8% vs 43.8%; P = 0.17), clinical pregnancy (44.1% vs 36.1%; P = 0.07) or pregnancy loss (11.8% vs 16.1%; P = 0.16). A multivariable analysis found no impact of timing of elective FET on LBR (odds ratio, OR 0.73; 95% CI 0.49-1.08). The impact remained not significant after adjusting for number of retrieved oocytes, drug used for ovulation trigger (hCG vs GnRH agonist) and reason for cryopreservation. The factors that significantly affected LBR were: maternal age in both age categories (women between 35 and 40 years vs women below 35 years, OR 0.63, 95% CI 0.4-0.95; and women over 40 years vs women below 35 years, OR 0.34, 95% CI 0.2-0.7), day of embryonic development at transfer (day +4 vs +3; OR 1.7, 95% CI 1.1-2.8) and number of transferred embryos (OR 2.2, 95% CI 1.4-3.3) and oestrogen used for endometrial preparation (transdermal vs oral; OR 0.62, 95% CI 0.4-0.9). LIMITATIONS REASONS FOR CAUTION The main limitation of our study is its retrospective nature. Although we adjusted our statistical analysis for a number of known and suspected confounders, we cannot exclude the possibility of residual confounding factors. WIDER IMPLICATIONS OF THE FINDINGS According to our results, clinicians might not need to wait more than one menstrual cycle before performing FET. This allows us to reduce unnecessary delays in FET, without compromising reproductive outcomes. STUDY FUNDING/COMPETING INTERESTS No funding was sought for this study. Authors declare no competing interests. TRIAL REGISTRATION NUMBER NA.

Objective: Progestin was recently used as an alternative of gonadotropin-releasing hormone (GnRH) analog for preventing premature luteinizing hormone (LH) surge with the aid of vitrification techniques, however, limited data were available about the potential of progestin in poor responders undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment. We performed a randomized parallel controlled trial to investigate the difference of progestin and GnRH antagonist in poor responders.Methods: A total of 340 poor responders who met with Bologna criteria were randomly allocated into the progestin-primed ovarian stimulation (PPOS) group and GnRH antagonist group. Fresh embryo transfer was preferred in the GnRH antagonist group and freeze-all was performed in the PPOS group. The primary outcome was the incidence of premature LH surge, secondary outcomes were the number of retrieved oocytes, the number of viable embryos and the pregnancy outcomes.Results: The results showed that the incidence of premature LH surge in PPOS group was lower than that in antagonist group (0 vs. 5.88%, P < 0.05). In PPOS group, the average numbers of oocytes and viable embryos were comparable to those in GnRH antagonist group (3.7 ± 2.6 vs. 3.4 ± 2.4; 1.6 ± 1.7 vs. 1.4 ± 1.3, P > 0.05), the live birth rate was similar between the two groups (21.8 vs. 18.2%, RR 1.25 (95% confidence interval 0.73, 2.13), P > 0.05).Conclusions: The study demonstrated that PPOS had a more robust control for preventing premature LH rise than GnRH antagonist in poor responders, but PPOS in combination with freeze-all did not significantly increase the probability of pregnancy than GnRH antagonist protocol for poor responders.

Endometriosis is an estrogen-dependent chronic inflammatory disease associated with pelvic pain symptoms that are often severe, mainly dysmenorrhea, nonmenstrual pelvic pain and dyspareunia. This condition is also associated with peripheral and central sensitization. The current medical treatment options for endometriosis-associated pain are limited. Recently, the US FDA approved the novel, oral, nonpeptide gonadotropin-releasing hormone antagonist elagolix for the management of moderate to severe endometriosis-associated pain. Elagolix produces dose-dependent estrogen suppression, from partial suppression at lower doses to nearly full suppression at higher doses. This review article summarizes the current understanding of the pathophysiology of endometriosis, with a focus on the role of estrogen and the mechanisms of pain symptoms, and reviews the clinical development of elagolix in women with endometriosis-associated pain.

To evaluate the effectiveness of delay start protocol in improving the success of in vitro fertilization (IVF) in poor responders according to Bologna's criteria. Only randomized controlled trial (RCT) of infertile women undergoing a single IVF/ICSI cycle with ovarian stimulation protocol based on daily injections with delay start protocol or a conventional antagonist protocol were included in this systematic review and meta-analysis. The review protocol was registered in PROSPERO before starting the data extraction (CRD42019128284). Primary outcome was clinical pregnancy rate. Ongoing pregnancy rate, miscarriage rate, number of oocytes, number of MII oocytes, stimulation length, gonadotropin amount and cancellation rate were considered as secondary outcomes. Four randomized controlled trials were included with a total number of 380 participants. 189 patients were included in the delayed start protocol and 191 were allocated to the comparison group. The results showed a significant higher clinical pregnancy rate (CPR) in patients allocated to the intervention. Data from all studies failed to detect a statistical difference between groups in terms of ongoing pregnancy rate (OPR), miscarriage rate (MR), Total-Oocyte, MII-Oocyte and Total-Embryos. Gonadotropin amount (GA) was significantly lower in the intervention group in comparison to controls, with no difference in stimulation length (SL) and cancelled cycle (CC). Delayed start GnRH-antagonist protocol may reduce GA and improve CPR in poor ovarian responder according to Bologna criteria.

The decapeptide hormone, Gonadotropin-Releasing Hormone (GnRH), induces gonadotropins (luteinizing hormone and folliclestimulating hormone) secretion from the anterior pituitary in an orderly way which is important for the control of gonadal function and normal ovarian cyclicity.

Introduction: We sought to address whether there are clinical responses when patients who are failing gonadotropin-releasing hormone (GnRH) agonist therapy are switched to degarelix. Androgen-deprivation therapy remains the backbone of treatment for disseminated prostate cancer and may be achieved with orchiectomy, GnRH agonists, or degarelix, a GnRH antagonist. Methods: To perform a systematic review and meta-analysis, a search of the BIOSIS Previews, Embase, International Pharmaceutical Abstracts, MEDLINE, and Google Scholar databases was performed using key terms. Quantitative meta-analysis was performed to provide a pooled estimate of prostate-specific antigen (PSA) response at three months. Results: Thirteen studies were identified, eight of which were included in the qualitative and quantitative analyses. Patient characteristics were broadly similar between the studies. Out of 155 patients across all included studies, 20 had stable PSA after the switch (12.9%), 14 had between 10‒30% decrease in PSA (9.0%), three had between 30‒50% decrease (1.9%), and 13 had more than 50% decrease (8.4%). Random effects meta-analysis of these data demonstrated a pooled response rate of 27.75 (95% confidence interval 18.9‒36.5%; I2=7.9%). Changes in testosterone levels following the switch could not be quantitatively assessed due to lack of sufficient data. Conclusions: Our results suggest that a switch to GnRH antagonist following progression on a GnRH agonist may result in a stable or decreased PSA at three months in about 30% of patients. This information should be considered among the potential options to discuss with patients with a rising PSA on GnRH agonist therapy.

The objective of this paper was to compare the effect of recombinant follicle-stimulating hormone (rFSH) and urinary follicle-stimulating hormone (uFSH) on pregnancy rates and live birth rates with the gonadotropin-releasing hormone (GnRH) antagonist protocol in China. This retrospective study was conducted from January 2014 through August 2017. Patients treated with uFSH had significantly higher levels of luteinizing hormone (3.79 mIU/ml vs. 3.09 mIU/ml) and progesterone (0.93 ng/ml vs. 1.16 ng/ml) on the day of human chorionic gonadotropin (HCG) administration, and they also had higher pregnancy rates (24.19% vs. 22.86%). There was no significant difference in the rate of live births. In the logistic regression results of the rFSH group, the pregnancy rate was positively correlated with the level of luteinizing hormone, with an odds ratio (OR) of 1.09 (95% confidence interval [CI]: 1.00–1.18; P = 0.048). In the uFSH group, the pregnancy rate was negatively correlated with the progesterone level on the day of HCG administration, with an OR of 0.47 (95% CI: 0.27–0.77; P = 0.004). Our research concluded that uFSH performed better than rFSH in terms of pregnancy rates when it was associated with the GnRH antagonist protocol. Meanwhile, no significant differences in the rate of live births were observed between the two groups.

Controlled ovarian stimulation (COS) with gonadotropins to produce multiple follicular development and high-quality oocytes is the cornerstone of assisted reproductive technology. Today, recombinant human follicle-stimulating hormone (r-hFSH) is widely used for COS. A long-acting r-hFSH and a combination of r-hFSH and recombinant human luteinizing hormone have recently become available. Formulations of purified urinary FSH with or without luteinizing hormone activity (provided by human chorionic gonadotropin) are also available. COS protocols can now be individualized to optimize efficacy and safety - defined as singleton pregnancies with a low incidence of ovarian hyperstimulation syndrome. This is facilitated by an estimation of ovarian response using the antral follicle count and/or serum anti-Müllerian hormone levels; anti-Müllerian hormone is viewed as the most reliable single marker. However, an efficient management strategy for poor responders to COS is still required. Developments in biomarkers and other techniques for accurate identification of viable oocytes and embryos and optimal uterine receptivity are expected.

Background Exogenous progestational agents have recently been introduced as an alternative pituitary modulator for the prevention of premature luteinizing hormone (LH) surges during in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments. There is increasing evidence that frozen-embryo transfer (FET) is associated with a lower risk of ovarian hyperstimulation syndrome (OHSS) in women with polycystic ovary syndrome (PCOS). Herein, we compared the clinical outcomes of the progesterone protocol with the gonadotropin releasing hormone antagonist (GnRH-ant) protocol in PCOS patients with a ''freeze-all'' strategy. Methods In this prospective single-central randomized controlled trial, a total of 120 PCOS patients undergoing their first IVF/ICSI treatment were randomly assigned to receive the progesterone protocol (study group) or GnRH-ant protocol (control group). The main outcome was the number of oocytes retrieved. Secondary outcomes included the incidence of premature LH rise/surge, the number of viable embryos, and pregnancy outcomes. Results The number of retrieved oocytes (14.65±7.64 versus 12.8±8.57) and viable embryos (5.38±3.54 versus 5.03±3.92) in the study group were comparable to those in the control group (P>0.05). Similarly, no between-group differences were found in the number of mature oocytes, fertilized oocytes, cleaved embryos, and the viable embryo rate per oocyte retrieved (P>0.05). However, the oocyte retrieval rate (66.02%±19.63% versus 54.38%±26.39%) and fertilization rate (78.12%±18.41% versus 62.76%±23.32%) in the study group were significantly more than that in the control group (P 0.05] and implantation rate [43.21% vs. 41.4%, RR 0.929 (95% CI: 0.595, 1.448), P>0.05] were also similar between the two groups. Conclusions The progesterone protocol is comparable with the GnRH-ant protocol regarding oocyte/embryo yields and the probability of clinical pregnancy in PCOS patients, but the two regimens were distinct in the regulation of pituitary LH secretion. Trial registration number Chictr.org.cn: ChiCTR-IOR-15006633.