Ovarian Stimulation Protocols Research Articles

Long GnRH Agonist versus GnRH Antagonist Protocols in Women with Endometrioma and Good Ovarian Reserve Undergoing IVF/ICSI Cycles

Background: The best ovarian stimulation protocol in the case of endometrioma-related infertility is still debated. In this study, we examined the effect of two ovarian stimulation protocols on in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) outcome in patients with good ovarian reserve suffering from endometrioma. Methods: In a retrospective study, 101 women with endometrioma and good ovarian reserve were recruited. Women received either gonadotropin-releasing hormone (GnRH) agonists (n=65) or GnRH antagonists (n=36) in an IVF or ICSI cycle. Clinical and chemical pregnancy rate, live birth rate, implantation rate, fertilization rate and fertilization proportion, as well as miscarriage rate, were evaluated in both groups. Results: Chemical (25% vs. 28.6%), clinical (19.6% vs. 25%), and live birth rates (19.6% vs. 25%) as well as implantation rate (11.7% vs. 15%) were not significantly different between the two groups. Miscarriage rate, fertilization rate and fertilization proportion were similar in the two groups. Conclusion: GnRH antagonist protocol with the main advantages of short duration and lower cost of treatment could be applied in infertile patients with endometrioma and good ovarian reserve.

Prothrombotic biomarkers during controlled ovarian stimulation for assisted reproductive technology

To assess the impact of 3 different ovarian stimulation protocols on surrogate biomarkers of coagulation. Observational multicenter cohort study. The study was conducted in assisted reproductive technology (ART) units. Infertile women undergoing ART in 2017-2019 were included. None. Our primary outcome was the endogenous thrombin potential (ETP) assessed by the calibrated automated thrombogram. The ETP was measured at baseline (T1), on the day of ovulation triggering (T2), and 7 days after triggering (T3). Three protocols were prescribed according to the standards used and without hormonal before treatment: agonist protocol with human chorionic gonadotropin (hCG) trigger (ag-hCG), antagonist protocol with hCG trigger (atg-hCG), or GnRH agonist trigger. The evolution of ETP was compared among groups using a mixed-effects linear regression model. Sixty-four women with a mean age of 37.8 years participated in the study: of which 24, 16, 24 received ag-hCG, atg-hCG, and GnRH agonist triggers, respectively. As expected, the mean serum estradiol levels in GnRH agonist trigger were statistically higher at T2 and lower at T3 than that for both ag-hCG and atg-hCG. Overall, the ETP evolution over time was statistically different between the groups. Values were similar between groups at T1 and increased at T2 in each group. The greatest difference occurred between T2 and T3 in each group. The ETP continued to increase at T3 in ag-hCG (+110 nM/L × min) and atg-hCG (+171 nM/L × min), but it remained stable in GnRH agonist trigger (-2 nM/L × min). Sex hormone-binding globulin showed persistent increase at T3 despite the fall in estradiol levels, particularly in the GnRH agonist trigger group. The ag-hCG and atg-hCG groups were associated with a higher hypercoagulable state at T3 than the GnRH agonist trigger group. However, our results show the persistence of a hypercoagulable state after the GnRH agonist triggering despite a sharp drop in estradiol levels. These findings may support the use of GnRH agonist trigger protocol in patients with high thrombotic risk and gives new insight into the fact that coagulation parameters could be disturbed for long time periods. NCT04188444.

Controlled ovarian stimulation for endometriosis patients with ultra-long GnRH-agonist or GnRH-antagonist protocols: A retrospective study by propensity score matching.

Although in vitro fertilization with embryo transfer is the most effective treatment for infertile patients with endometriosis, ovarian stimulation protocols are controversial. We recruited 639 patients with endometriosis from January 2016 to June 2020; 111 and 528 patients were treated with the gonadotropin-releasing hormone (GnRH) antagonist and ultra-long GnRH agonist protocols, respectively. Potential baseline differences between the regimens were adjusted by propensity score matching. Clinical and laboratory data, including the cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR), were compared. Ovulation induction required significantly longer use of gonadotropins in the GnRH agonist group. However, the GnRH agonist group had a lower starting dose of gonadotropin (all p < 0.05). Furthermore, significantly lower clinical pregnancy, implantation, and live birth rates were observed in the GnRH antagonist group receiving fresh assisted reproductive technology cycles (all p < 0.05); however, pregnancy outcomes using the subsequent freeze-thaw cycles for the same oocyte retrieval were not significantly different. CCPR and CLBR for the oocyte retrieval cycles of the antagonist and ultra-long agonist protocols were similar. The ultra-long agonist protocol resulted in more favorable implantation of fresh embryos and improved clinical outcomes of the fresh cycle. This novel strategy could be appropriate for endometriosis patients who are temporarily unsuitable for fresh embryo transfer. The GnRH antagonist protocol can be combined with the whole embryo freezing strategy to achieve CCPR and CLBR similar to the ultra-long agonist regimen, thus simultaneously avoiding the long pre-treatment duration of GnRH agonists during the ultra-long agonist protocol.

Use of gonadotropins in ovarian stimulation in Spain: Delphi consensus

Two-round Delphi study carried out in Spain. Three theme-based blocks were set out: 1) Patient profiles: therapeutic goal and parameters to be analysed according to POSEIDON patient profiles; 2) Ovarian stimulation protocols with antagonists: monotherapy (FSH) vs combined therapy (FSH + LH/HMG); 3) Safety and effectiveness of the devices. The antral follicle count and the anti-Müllerian hormone level were considered indicators that can be used to predict ovarian response. More than 80% of the participants agreed that FSH monotherapy is the recommended regimen in normal/hyper-responsive patients of < 35 years of age; that 150–300 IU is the dose to be used in ovarian stimulation in monotherapy depending on clinical parameters; and that FSH monotherapy improves patients’ comfort compared to two combined drugs. It was unanimously considered that the type of device used by the patient influences the comfort of the treatment. IMPACT STATEMENT What is already known on this subject? There is currently no consensus on the optimal treatment for controlled ovarian stimulation for patients undergoing IVF which leads to highly variable clinical practices. What the results of this study add? This study’s strong point is that, since it is a consensus, it has been possible to include more topics than would normally be dealt with in a systematic review or guidelines, which are generally based on a strict method that restricts the scope of the research. Experts have reached a consensus on most of the statements and based on these they have issued consensus statements that will enable the optimal use of gonadotropins in IVF. What the implications are of these findings for clinical practice and/or further research? This Delphi consensus provides a real-life clinical perspective on gonadotropin usage in IVF.

Soft ovarian stimulation protocol in polycystic ovary syndromes women inspired by gonadotropin stimulated intrauterine insemination cycles converted to rescue IVF: time to shift the focus “retrospective study”

BackgroundPolycystic ovary syndrome (PCOs) women usually exhibit a high luteinizing hormone (LH) and hypersensitivity to exogenous gonadotropins stimulation which is a tremendous risk to ovarian hyperstimulation syndrome (OHSS). Since the pathophysiology of PCOS is mysterious, an aetiological approach to the treatment is difficult and should be individually designed. These features affect the outcome of treatment including ovulation and success rate. Also, PCOS women who have difficulty conceiving, frequently experience substantial treatment burden, risk, and psychological distress. Recently, a renewed interest has emerged in patient-friendly, low-risk, and less costly IVF treatments. Our study proposed a new soft protocol in PCOS ovrian stimulation without prior pituitary desensitization followed by fresh embryo transfer. Patients and methods: a retrospective cohort study was conducted between January 2018 to December 2021, including 48 out of 325 women with PCOS who underwent gonadotropin-stimulated intrauterine insemination cycles but due to unexpectedly high response with risk of multiple pregnancies and OHSS, they had been shifted to a rescue IVF and fresh embryo transfer. The primary outcomes were biochemical pregnancy, implantation rate, clinical pregnancy, rate of miscarriage, OHSS, and multiple pregnancies. Secondary outcomes were the endocrinological profiles, gonadotropin dose, and duration of stimulation. This study aims to evaluate the outcomes in the conversion of high-response gonadotropin intrauterine insemination (IUI) cycles to “rescue” in vitro fertilization (IVF/fresh embryo transfer) regarding implantation rates, pregnancy rates, and ovarian hyperstimulation syndrome (OHSS).ResultsThis study used a low dose gonadotropin injections (2.1 ± 1.4) for an average duration of (9.1 ± 1.2) and showed a high success pregnancy rate: biochemical pregnancies (56.2%), implantation rate (50.2%), clinical pregnancy rate (49.9%), and miscarriage rate (8.5%). Multiple pregnancies occurred in (6.6%) and OHSS(4.4%) only in a mild form.ConclusionOur study revealed that ovarian stimulation without prior pituitary suppression in high responders was feasible to improve the implantation rate and alleviate profound OHSS without compromising the pregnancy outcomes. This encourages all fertility specialists to implement this new protocol with expected high responders as an alternative to the conventional cycle segmentation protocol: GnRH agonist-antagonist IVF/freeze-all strategy.

Is the long-acting gonadotropin-releasing hormone agonist longprotocol better for patients with endometriosis undergoing IVF?

To investigate the effect of the long-acting gonadotropin-releasing hormone agonist (GnRHa) long protocol on in vitro fertilization (IVF) outcomes of patients with endometriosis (EMs). This retrospective cohort study was carried out from July 1, 2016 to June 30, 2021. In all, 798 patients with EMs who underwent first IVF were enrolled. The patients were classified by the ovarian stimulation protocols. The clinical outcomes of IVF were compared in each group. Those EMs patients who received the long-acting GnRHa long protocol had significantly higher clinical pregnancy rate (72.00%, 60.70% and 50.90%, respectively; P= 0.047 and 0.010) and implantation rate (51.0%, 44.6%, and 38.7%, respectively; P= 0.006 and <0.001) compared with the short-acting GnRHa long protocol and the GnRH antagonist protocol. Live birth rate was also significantly higher than the GnRH antagonist protocol (60.10% vs. 40.0%, P= 0.032), but not statistically different from the short-acting GnRHa (60.10% vs. 53.80%, P= 0.443). In addition, they also had significantly higher duration of stimulation, total dose of gonadotropin, and number of high-quality embryos transferred compared with other groups (P< 0.001). The long-acting GnRHa long protocol could improve IVF outcomes of patients with EMs compared with the short-acting GnRHa long protocol and the GnRH antagonist protocol.

Freeze-all embryos during treatment with assisted reproduction: Health economic aspects.

Assisted reproductive technologies are evolving, with the most recent example being the introduction of the freeze-all policy during which a fresh embryo transfer does not take place and all embryos of good quality are cryopreserved to be used in future frozen embryo transfers. As the freeze-all policy is becoming more prevalent, it is important to review the economic aspects of this approach, along with considerations of efficacy and safety, and the role of emerging freeze-all-specific ovarian stimulation strategies. Based on the available evidence, the freeze-all policy presents distinct clinical advantages, particularly for high responders. Available health economic evaluations are limited. Two good-quality cost-effectiveness analyses based on randomized controlled trials suggest that the freeze-all strategy is unlikely to be cost-effective in non-polycystic ovarian syndrome (non-PCOS), normally responding patients. However, the cost-effectiveness of the freeze-all strategy in different populations of patients and in different settings has not been evaluated, nor has the clinical and economic efficacy of modern freeze-all-specific ovarian stimulation protocols that are likely to simplify treatment and make it more affordable for patients. Economic evaluations that incorporate good practice health technology assessment (HTA) methods are needed to compare freeze-all with conventional embryo transfer strategies. Furthermore, future research should address the unique limitation of traditional HTA methods in valuing a life conceived through fertility treatment.

Analysis of euploidy rates in preimplantation genetic testing for aneuploidy cycles with progestin-primed versus GnRH agonist/antagonist protocol

BackgroundProgestins can suppress endogenous luteinising hormone (LH) secretion from the pituitary gland and have shown similar efficacy in terms of collecting competent oocytes and embryos; however, some inconsistencies have been proposed regarding the quality of embryos collected with the use of progestins. This study aimed to evaluate euploidy rates and pregnancy outcomes in preimplantation genetic testing for aneuploidy (PGT-A) cycles using the progestin-primed ovarian stimulation (PPOS) protocol versus the gonadotropin-releasing hormone (GnRH) agonist/antagonist protocol.MethodsThis retrospective cohort study included 608 PGT-A cycles: 146 women in the PPOS group, 160 women in the GnRH agonist group, and 302 women in the GnRH antagonist group. This study was performed at the in vitro fertilisation (IVF) centre of Shanghai First Maternity and Infant Hospital between January 2019 and December 2021. Additionally, 267 corresponding first frozen embryo transfer (FET) cycles were analysed to assess pregnancy outcomes.ResultsThe euploid blastocyst rate per injected metaphase II(MII) oocytes (14.60% vs. 14.09% vs. 13.94%) was comparable among the three groups (p > 0.05). No significant differences were observed among the three groups regarding pregnancy outcomes, including biochemical pregnancy, clinical pregnancy, ongoing pregnancy, implantation, miscarriage, ectopic pregnancy, and live birth rates per transfer in the first FET cycles (p > 0.05).ConclusionsThe PPOS protocol had no negative effect on euploid blastocyst formation, and the pregnancy outcomes in FET cycles using the PPOS protocol were similar to those of the GnRH agonist and antagonist protocols.Trial registration This trial was retrospectively registered

Does mRNA COVID-19 vaccination in oocyte donors impact ovarian stimulation parameters or IVF outcomes for recipients?

Research questionWhat is the effect of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in young oocyte donors in terms of ovarian response to stimulation, fertilization rate, embryo development and clinical outcomes in recipients? DesignThis retrospective, multicentre cohort study evaluated 115 oocyte donors who had undergone at least two ovarian stimulation protocols (before and after complete SARS-CoV-2 vaccination) between November 2021 and February 2022. Comparisons were made of the primary outcomes of days of stimulation, total dose of gonadotrophins and laboratory performance in ovarian stimulation in oocyte donors before and after vaccination. A total of 136 cycles in matched recipients were analysed as secondary outcomes and, from those, 110 women received a fresh single-embryo transfer, with analysis of biochemical β-human chorionic gonadotrophin concentrations and rates of clinical pregnancy with heartbeat. ResultsLonger stimulation was required in the post-vaccination than pre-vaccination group (10.31 ± 1.5 versus 9.51 ± 1.5 days; P < 0.001) along with higher gonadotrophin consumption (2453.5 ± 740 versus 2235.5 ± 615 IU; P < 0.001) with a similar starting dose of gonadotrophins in both groups. More oocytes were retrieved in the post-vaccination group (16.62 ± 7.1 versus 15.38 ± 7.0; P = 0.02). However, the number of metaphase II (MII) oocytes was similar between groups (pre-vaccination 12.61 ± 5.9 versus post-vaccination 13.01 ± 6.6; P = 0.39) and the ratio of MII/retrieved oocytes favoured the pre-vaccination group (0.83 ± 0.1 versus 0.77 ± 0.2 post-vaccination; P = 0.019). In recipients with a similar number of provided oocytes, the fertilization rate, total number of obtained blastocysts, number of top-quality blastocysts, and rates of biochemical pregnancy and clinical pregnancy with heartbeat were not significantly different between groups. ConclusionsThis study shows no adverse influence of mRNA SARS-CoV-2 vaccination on ovarian response in a young population.

What is the optimal GnRH antagonist protocol for ovarian stimulation during ART treatment? A systematic review and network meta-analysis.

Several GnRH antagonist protocols are currently used during COS in the context of ART treatments; however, questions remain regarding whether these protocols are comparable in terms of efficacy and safety. A systematic review followed by a pairwise and network meta-analyses were performed. The systematic review and pairwise meta-analysis of direct comparative data according to the PRISMA guidelines evaluated the effectiveness of different GnRH antagonist protocols (fixed Day 5/6 versus flexible, ganirelix versus cetrorelix, with or without hormonal pretreatment) on the probability of live birth and ongoing pregnancy after COS during ART treatment. A frequentist network meta-analysis combining direct and indirect comparisons (using the long GnRH agonist protocol as the comparator) was also performed to enhance the precision of the estimates. The systematic literature search was performed using Embase (Ovid), MEDLINE (Ovid), Cochrane Central Register of Trials (CENTRAL), SCOPUS and Web of Science (WOS), from inception until 23 November 2021. The search terms comprised three different MeSH terms that should be present in the identified studies: GnRH antagonist; assisted reproduction treatment; randomized controlled trial (RCT). Only studies published in English were included. The search strategy resulted in 6738 individual publications, of which 102 were included in the systematic review (corresponding to 75 unique studies) and 73 were included in the meta-analysis. Most studies were of low quality. One study compared a flexible protocol with a fixed Day 5 protocol and the remaining RCTs with a fixed Day 6 protocol. There was a lack of data regarding live birth when comparing the flexible and fixed GnRH antagonist protocols or cetrorelix and ganirelix. No significant difference in live birth rate was observed between the different pretreatment regimens versus no pretreatment or between the different pretreatment protocols. A flexible GnRH antagonist protocol resulted in a significantly lower OPR compared with a fixed Day 5/6 protocol (relative risk (RR) 0.76, 95% CI 0.62 to 0.94, I2 = 0%; 6 RCTs; n = 907 participants; low certainty evidence). There were insufficient data for a comparison of cetrorelix and ganirelix for OPR. OCP pretreatment was associated with a lower OPR compared with no pretreatment intervention (RR 0.79, 95% CI 0.69 to 0.92; I2 = 0%; 5 RCTs, n = 1318 participants; low certainty evidence). Furthermore, in the network meta-analysis, a fixed protocol with OCP resulted in a significantly lower OPR than a fixed protocol with no pretreatment (RR 0.84, 95% CI 0.71 to 0.99; moderate quality evidence). The surface under the cumulative ranking (SUCRA) scores suggested that the fixed protocol with no pretreatment is the antagonist protocol most likely (84%) to result in the highest OPR. There was insufficient evidence of a difference between fixed/flexible or OCP pretreatment/no pretreatment interventions regarding other outcomes, such as ovarian hyperstimulation syndrome and miscarriage rates. Available evidence, mostly of low quality and certainty, suggests that different antagonist protocols should not be considered as equivalent for clinical decision-making. More trials are required to assess the comparative effectiveness of ganirelix versus cetrorelix, the effect of different pretreatment interventions (e.g. progestins or oestradiol) or the effect of different criteria for initiation of the antagonist in the flexible protocol. Furthermore, more studies are required examining the optimal GnRH antagonist protocol in women with high or low response to ovarian stimulation.

Factors Influencing the Pregnancy Outcome of Intrauterine Insemination and Follow-up Treatment.

Many factors were reported associated with the pregnancy rate of intrauterine insemination (IUI), which played key role is still debated. The aim of this study was to explore related clinical pregnancy outcome factor in IUI cycles of non-male factor. The clinical data of 1232 IUI cycles in 690 couples experiencing infertility who attended the Reproductive Center of Jinling Hospital between July 2015 and November 2021 were retrospectively analysed. Female and male age, body mass index (BMI), anti-Müllerian hormone (AMH), male semen parameters before and after wash, endometrial thickness (EMT), artificial insemination timing and ovarian stimulation (OS) protocols were compared between the pregnant group and the non-pregnant group in order to explore any correlation. Continuous variables were analysed using independent-samples t-test, and Chi-square test was used for comparison of measurement data between the two groups. P <0.05 was considered statistical significance. There were statistically significant differences in female AMH, EMT and duration of OS between the two groups. The AMH was higher in the pregnant group than in the non-pregnant group (P < 0.01), the stimulated days was significantly longer (P < 0.05) and EMT was significantly greater (P < 0.01) in the pregnant group than in the non-pregnant group. Further analysis showed that when patients with IUI had the following conditions: AMH &gt; 4.5 ng/ml, EMT between 8 and 12 mm and letrozole + human menopausal gonadotropin stimulation with higher clinical pregnancy. However, there were no differences between the pregnant group and the non-pregnant group amongst the female and male age, BMI, hormones on baseline and day of human chorionic gonadotrophin, number of ovulated oocytes, sperm parameters before and after wash, treatment protocols and the timing of IUI (P > 0.05). Furthermore, there were 240 couples who not pregnant received one or more cycles of in vitro fertilisation/intracytoplasmic sperm injection/ pre-implantation genetic technology treatment, and another 182 couples forgo follow-up treatment. The results of the present study demonstrate that the clinical IUI pregnancy rate is correlated with the factors of female AMH, EMT and OS protocol; more studies and samples are necessary to evaluate whether other factors affect pregnancy rate.

Comparing ART outcomes in women with endometriosis after GnRH agonist versus GnRH antagonist ovarian stimulation: a systematic review.

Endometriosis is an oestrogen-dependent disease that can cause subfertility in women who may require assisted reproductive technology (ART) to achieve their pregnancy goals. The aim of this study was to compare ART outcomes in women with endometriosis following the long GnRH-agonist controlled ovarian stimulation (COS) protocol with those taking the GnRH-antagonist COS protocol. MEDLINE, Embase and Web of Science were systematically searched in June 2022. Randomized controlled trials (RCTs) and observational studies comparing the long GnRH-agonist COS protocol and the GnRH-antagonist COS protocol in women with all stages/subtypes of endometriosis were included. Data were synthesized into comprehensive tables for systematic review. The Scottish Intercollegiate Guidelines Network (SIGN) checklists were used for the risk of bias assessment of non-randomized studies and randomized studies, and all the included studies were deemed to have acceptable quality. Eight studies (one RCT and seven observational) with 2695 patients (2761 cycles) were included. Most studies generally reported non-significant differences in clinical pregnancy or live birth rates regardless of the COS protocol used. However, the GnRH-agonist protocol may yield a higher total number of oocytes retrieved, especially mature oocytes. Conversely, the GnRH-antagonist protocol required a shorter COS duration and lower gonadotrophin dose. Adverse outcomes, such as rates of cycle cancellation and miscarriage, were similar between both COS protocols. Both the long GnRH-agonist and GnRH-antagonist COS protocols generally yield similar pregnancy outcomes. However, the long GnRH-agonist protocol may be associated with a higher cumulative pregnancy rate due to the higher number of retrieved oocytes available for cryopreservation. The underlying mechanisms of the two COS protocols on the female reproductive tract remain unclear. Clinicians should consider treatment costs, stage/subtype of endometriosis and pregnancy goals of their patients when selecting a GnRH analogue for COS. A well-powered RCT is needed to minimize the risk of bias and compare the risk for ovarian hyperstimulation syndrome. This review was prospectively registered at PROSPERO under Registration No. CRD42022327604.

Why do we Modify Ovarian Stimulation Protocols when Repeating a Cycle?” Is it a Scientific Issue, An act of Faith, or a Lack of Trust?

Ovarian Stimulation (OS) is a cornerstone and indispensable step in reproductive medicine. The aim of OS is to induce the growth and maturation of multiple follicles to collect an adequate number of oocytes. The availability of a sufficient number of mature oocytes suitable for in vitro fertilization (IVF) significantly enhances the likelihood of successful fertilization, the development of high-quality euploid embryos, and ultimately, the achievement of a successful pregnancy. Frequently, it becomes necessary to repeat an ovarian stimulation procedure in a patient. In some instances, when faced with a poor ovarian response, the strategy of oocyte accumulation is employed to increase the chances of having a euploid blastocyst available for transfer. Moreover, even among good responders, there are occasions where it becomes necessary to repeat a cycle due to a prior unsuccessful attempt. The present study shows that there is a great variability in ovarian response in successive ovarian stimulation procedures, even administering the same protocol, both in terms of doses and medications. Thus, repeating an ovarian stimulation procedure does not necessarily entail the need to modify the stimulation protocol. There is variability in ovarian response even when the same gonadotropins are administered, as shown in the present study. Hence, in consecutive stimulations, variations in the response are physiological, even though the same protocol and medication are employed. Selecting one protocol over another should prioritize the comfort and convenience of the patient rather than a hypothetical improved response with different medications.

Corifollitropin Alfa for Controlled Ovarian Stimulation in Assisted Reproductive Technologies: State of the Art.

Physical and emotional burdens during the journey of infertile people through assisted reproductive technologies are sufficient to justify the efforts in developing patient-friendly treatment strategies. Thus, shorter duration of ovarian stimulation protocols and the need for less injections may improve adherence, prevent mistakes, and reduce financial costs. Therefore, the sustained follicle-stimulating action of corifollitropin alfa may be the most differentiating pharmacokinetic characteristic among available gonadotropins. In this paper, we gather the evidence on its use, aiming to provide the information needed for considering it as a first choice when a patient-friendly strategy is desired.

Progestin-primed ovarian stimulation protocol with or without clomiphene citrate for poor ovarian responders: a retrospective cohort study

ObjectiveTo explore the efficacy of progestin-primed ovarian stimulation (PPOS) combined with clomiphene citrate (CC) versus PPOS protocol used alone on cycle characteristics and pregnancy outcomes for women with the poor ovarian response (POR).MethodsWe performed a retrospective cohort study and a total of 578 POR patients who underwent IVF/ICSI cycles were collected and divided into Group A (HMG 300 IU/d + MPA 10 mg/d) and Group B (HMG 300 IU/d + MPA 10 mg/d + CC 50 mg/d). The primary outcome measure was the number of oocytes retrieved, other outcome measures were cycle characteristics and clinical pregnancy rate.ResultsThe baseline information between the two groups were not statistically significant (P > 0.05). Compared with Group A, Group B had a lower total dose of human menopausal gonadotrophin (HMG) (2998.63 ± 1051.09 vs. 3399.18 ± 820.75, P < 0.001) and the duration of stimulation (10.21 ± 3.56 vs. 11.27 ± 2.56, P < 0.001). Serum luteinizing hormone level was higher in Group B on human chorionic gonadotrophin injection day (P < 0.001). The number of oocyte for retrieval, maturation, and fertilization were significantly lower in Group B than that in Group A (P < 0.001). However, the oocyte retrieval rate, maturation rate, fertilization rate, and viable embryo rate showed no statistical difference in the two groups (P > 0.05). After adjusting for confounders, the clinical pregnancy rate (OR 1.286; 95% CI 0.671–2.470) and live birth rate (OR 1.390; 95% CI 0.478–3.990) were comparable between the two groups.ConclusionsPPOS protocol combined with CC reduces the total dose of HMG and the duration of stimulation, and can also achieve similar oocyte yields and clinical pregnancy rate compared with the PPOS protocol used alone in poor ovarian responders.

Are Early Embryo Cleavage Kinetics Affected by Energy Substrates in Different Culture Media?

This study aimed to investigate the influence of different culture media on early embryonic cleavage kinetics using time-lapse analysis and to determine the possible relationships between energy substrates in culture media and the cleavage kinetics. A total of 10 021 embryos from 1310 couples were cultured in time-lapse incubators. Embryos cultured in Vitrolife media were allocated to group I, and those in COOK media to group II. Embryo cleavage time points up to the 8-cell stage (t2-t8) were observed after pronuclei fading. The baseline demographic features, in vitro fertilization indications, ovarian stimulation protocol, oocyte-cumulus complexes, fertilization rate, together with pregnancy and perinatal outcomes were similar (P>0.05) between groups I and II. According to the time-lapse analysis, all embryos in group I showed significantly faster cleavage speed than those in group II (P<0.05). Furthermore, there was better synchrony in division (s3) and a longer length of the third cell cycle duration (cc3) in group II. Interestingly, implanted embryos in group II showed faster cleavage speed than those in group I, especially at t4 and t7. The glucose contents and multiple major amino acids were similar between the two groups. Lactic and pyruvic acid contents were generally higher in group I than those in group II. Because different commercial culture media may influence cleavage kinetics of embryos, it is essential for embryologists to take culture media into consideration in selecting a potential embryo when using a time-lapse system before implantation.

Slightly Elevated Progesterone on HCG Trigger Day Has an Impact on Pregnancy Outcomes of Fresh Single Blastocyst Transfer Cycles Under an Early Follicular Phase Prolonged Protocol Cycle.

The effect of premature progesterone elevation on assisted reproductive technology has been debated. In different ovarian stimulation protocols, ovarian responses, and embryos transferred, conflicting results reside regarding the impact of elevated progesterone on pregnancy outcomes, according to previous studies. In addition, most studies have focused on significantly elevated progesterone levels, eg, above 1.5ng/mL, 1.75ng/mL, 2ng/mL. However, studies focusing on levels that are just slightly elevated are lacking, and some have concluded that such levels have no adverse effects on pregnancy outcomes. Clinical data of patients who underwent early follicular phase prolonged protocol cycle in vitro fertilization/intracytoplasmic sperm injection treatment were collected. Patients were divided into two groups according to progesterone level on the trigger day of human chorionic gonadotropin (HCG): Group 1: <1.0ng/mL and Group 2: 1.0-1.5ng/mL. Differences in baseline characteristics, ovulation promotion, and embryo culture, along with clinical pregnancy outcomes, were compared between the two cohorts. A total of 743 participants were included in this study, of which 587 were included in Group 1 and 156 were included in Group 2. In terms of pregnancy outcomes, Group 2 had a significantly lower clinical pregnancy rate and live birth rate per cycle than Group 1 (64.1% vs 75.7%, p <0.05; 63.5% vs 72.7%, p <0.05). After correction for maternal age, maternal body mass index, infertility duration, basal follicle-stimulating hormone, anti-Müllerian hormone, antral follicle count, total dose of gonadotropin, days of stimulation, and estradiol level on HCG trigger day, slightly elevated progesterone levels (P>1.0ng/mL) remained a risk factor for pregnancy failure in fresh single D5 blastocyst transfer under an early follicular phase prolonged protocol cycle. Slightly elevated progesterone levels on HCG trigger day may negatively affect pregnancy outcomes in early follicular phase prolonged protocol cycles.

ПЕРСОНИФИЦИРОВАННЫЙ ПОДХОД К ОВАРИАЛЬНОЙ СТИМУЛЯЦИИ У ПАЦИЕНТОК С ПАРАДОКСАЛЬНЫМ ОТВЕТОМ В ПРОГРАММАХ ЭКО

Presented are current data on the need to identify the main groups of patients in in vitro fertilization programs that require a personalized protocol for ovarian stimulation and modification of traditional ovarian stimulation protocols in in vitro fertilization programs. The influence of polymorphism of gonadotropin receptor genes on the ovarian response during superovulation induction was shown.

Hormonal parameters and embryological outcomes of in vitro fertilisation/intra cytoplasmic sperm injection cycles in women using dydrogesterone for the prevention of premature luteinizing hormone surge during ovarian stimulation

Aim. To evaluate the hormonal parameters and embryological outcomes of an ovarian stimulation protocol using dydrogesterone to prevent the premature LH surge in IVF/ICSI programmes.&#x0D; Materials and methods. A prospective study randomised, including 79 women with normal ovarian reserve undergoing ovarian stimulation for IVF/ICSI with recombinant FSH (rFSH) from Day 2 or 3 of the menstrual cycle. To prevent the premature LH surge, participants in Group 1 (n=38) received oral dydrogesterone 20 mg/day from the start of ovarian stimulation until the day of ovulation trigger administration. Participants in Group 2 (n=41) received a GnRH antagonist. We evaluated the starting and total dose of gonadotropins, duration of stimulation, serum levels of LH, oestradiol and progesterone on Day 1 and 6 of stimulation and the day of trigger administration, number of retrieved and mature oocytes, fertilization rate, and the number of blastocysts and cryopreserved embryos.&#x0D; Results. There were no significant differences in most hormonal parameters, characteristics of the ovarian stimulation and embryological outcomes between the two groups. Serum levels of progesterone in the dydrogesterone arm were higher than in the GnRH antagonist arm (2.3 nmol/l [2.03.4] vs 1.5 [1.02.4] nmol/l; p=0.026), but without any impact on the embryological outcomes.&#x0D; Conclusion. Prevention of premature LH surge in ovarian stimulation cycles using oral dydrogesterone may represent a convenient alternative to the conventional use of GnRH antagonists, reducing the number of required injections and potentially increasing the convenience in patients who are not planning a fresh embryo transfer.

Risk of thrombosis in women with cancer undergoing controlled ovarian hyperstimulation for fertility preservation.

The study aims to evaluate the risk factors and incidence of thromboembolic events among adult women with cancer who underwent controlled ovarian hyperstimulation (COH) for fertility preservation. Retrospective, descriptive cohort analysis of patient demographics, medical history, cancer type/treatment, laboratory values, thrombosis within 6months of COH. 4 of 127 study participants experienced a venous thromboembolic event within 6months of COH. The median time between oocyte aspiration and the event was 0.25years (range = 0.10-0.50). The average age at time of event was 25.3years (SD = 5.3). Three of four thrombotic patients had ovarian cancer, one had breast cancer. All had received surgery and chemotherapy for treatment. All underwent an antagonist cycle ovarian stimulation protocol - none developed ovarian hyperstimulation syndrome. The average anti-mullerian hormone level at the time of hyperstimulation in the thrombosis group was 1.6 (SD = 1.3), compared to 3.6 in the non-thrombosis group. The average max estradiol level reached during ovarian stimulation was 1281.3 (SD = 665.3) in the thrombosis group and 1839.1 (SD = 1513.9) in the non-thrombosis group. Thromboembolic events were not directly associated with mortality. Within this small descriptive study, the incidence of thromboembolic events in women with cancer undergoing COH for fertility preservation is high. Cancer may play a greater role than COH in thrombosis risk. Ovarian cancer patients who undergo ovarian stimulation may have an increased risk compared to other cancer types. These findings may inform future, prospective studies to determine the role of thromboprophylaxis.