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Premature progesterone rise during gonadotrophin-releasing hormone (GnRH) antagonist cycles for IVF is a frequent phenomenon and has been associated with lower pregnancy and implantation rates. This study evaluated endometrial gene expression on the day of oocyte retrieval according to the concentration of serum progesterone on the day of human chorionic gonadotrophin (HCG) administration in GnRH-antagonist/recombinant FSH IVF cycles with fresh embryo transfer. Endometrial biopsies (n=14) were analysed with Affymetrix HG U133 Plus 2.0 Arrays. Patients were divided into three groups according to their progesterone serum concentration on the day of HCG administration: ≤ 0.9 ng/ml (group A), 1-1.5 ng/ml (group B) and >1.5 ng/ml (group C). Gene expression analysis showed a small number of significantly differentially expressed probe sets between groups A and B (five up/23 down in B) and a large difference between groups B and C (607 up/212 down; P ≤ 0.05, fold change ≥ 1.4). Validation was performed with quantitative real-time PCR on selected genes. As far as is known, this is the first study to demonstrate a distinct difference in endometrial gene expression profile between patients with a progesterone serum concentration above and below the threshold of 1.5 ng/ml on the day of HCG administration., (Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

To date, limited data exist concerning the relation between endometrial thickness on the day of human chorionic gonadotrohin (HCG) administration and ongoing pregnancy achievement in cycles stimulated with clomiphene citrate for intrauterine insemination (IUI). In a prospective study, 168 couples were stimulated with clomiphene citrate from day 3 to day 7 of the cycle and endometrial thickness was assessed by ultrasound three times on the day of ovulation triggering. Ovulation was induced with HCG as soon as >/=1 follicle of >/=17 mm was present at ultrasound independently of endometrial thickness. IUI was performed 36 h after HCG administration. The main outcome measure was ongoing pregnancy. No difference was observed in endometrial thickness between patients who did or did not achieve an ongoing pregnancy (7.6 +/- 0.3 versus 7.6 +/- 0.2 respectively; P = 0.7). No discriminative ability of endometrial thickness on the achievement of ongoing pregnancy could be shown by receiver operating characteristic (ROC) curve analysis (area under the ROC curve 0.51, 95% CI: 0.44-0.59). In conclusion, endometrial thickness cannot predict ongoing pregnancy achievement in IUI cycles stimulated with clomiphene citrate.

Objective: To evaluate whether trigger and oocyte collection at a smaller follicle size decreases the risk of premature ovulation while maintaining the reproductive potential of oocytes in women with a severely diminished ovarian reserve undergoing modified natural‐cycle in‐vitro fertilization. Methods: This was a retrospective cohort study including women who had at least one unsuccessful cycle (due to no response) of conventional ovarian stimulation with a high dosage of gonadotropins and subsequently underwent a modified natural cycle with a solitary growing follicle (i.e. only one follicle > 10 mm at the time of trigger). The association between follicle size at trigger and various cycle outcomes was tested using regression analyses. Results: A total of 160 ovarian stimulation cycles from 110 patients were included in the analysis. Oocyte pick‐up (OPU) was performed in 153 cycles and 7 cycles were canceled due to premature ovulation. Patients who received their trigger at smaller follicle sizes (≤ 15 mm) had significantly lower rates of premature ovulation and thus higher rates of OPU (98.9% vs 90.8%; odds ratio, 9.56 (95% CI, 1.58–182.9); P = 0.039) compared with those who received their trigger at larger follicle sizes (> 15 mm). On multivariable analysis, smaller follicle sizes at trigger (> 10 to 13 mm, > 13 to 15 mm, > 15 mm to 17 mm) were not associated significantly with a lower rate of cumulus–oocyte complex (COC) retrieval, metaphase‐II (MII) oocytes or blastulation when compared to the > 17‐mm group. On sensitivity analysis including only the first cycle of each couple, the maturity rate among those with COC retrieval was highest in follicle sizes > 15 to 17 mm (92.3%) and > 13 to 15 mm (91.7%), followed by > 10 to 13 mm (85.7%) and lowest in the > 17‐mm group (58.8%). During the study period, five euploid blastocysts developed from 48 fertilized MII oocytes with follicle sizes of 12 mm (n = 3), 14 mm (n = 1) and 16 mm (n = 1) at trigger. Of those, four were transferred and resulted in two live births, both of which developed from follicles with a size at trigger of 12 mm. Conclusions: The ideal follicle size for triggering oocyte maturation may be smaller in women with a severely diminished ovarian reserve managed on a modified natural cycle when compared to conventional cut‐offs. The risk of OPU cancellation was significantly higher in women triggered at follicle size > 15 mm and the yield of mature oocytes was not adversely affected in women triggered at follicle size > 13 to 15 mm compared with > 15 to 17 mm. Waiting for follicles to reach sizes > 17mm may be detrimental to achieving optimal outcome. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Purpose: To provide agreed-upon guidelines on the management of a hyper-responsive patient undergoing ovarian stimulation (OS) Methods: A literature search was performed regarding the management of hyper-response to OS for assisted reproductive technology. A scientific committee consisting of 4 experts discussed, amended, and selected the final statements. A priori, it was decided that consensus would be reached when ≥66% of the participants agreed, and ≤3 rounds would be used to obtain this consensus. A total of 28/31 experts responded (selected for global coverage), anonymous to each other. Results: A total of 26/28 statements reached consensus. The most relevant are summarized here. The target number of oocytes to be collected in a stimulation cycle for IVF in an anticipated hyper-responder is 15–19 (89.3% consensus). For a potential hyper-responder, it is preferable to achieve a hyper-response and freeze all than aim for a fresh transfer (71.4% consensus). GnRH agonists should be avoided for pituitary suppression in anticipated hyper-responders performing IVF (96.4% consensus). The preferred starting dose in the first IVF stimulation cycle of an anticipated hyper-responder of average weight is 150 IU/day (82.1% consensus). ICoasting in order to decrease the risk of OHSS should not be used (89.7% consensus). Metformin should be added before/during ovarian stimulation to anticipated hyper-responders only if the patient has PCOS and is insulin resistant (82.1% consensus). In the case of a hyper-response, a dopaminergic agent should be used only if hCG will be used as a trigger (including dual/double trigger) with or without a fresh transfer (67.9% consensus). After using a GnRH agonist trigger due to a perceived risk of OHSS, luteal phase rescue with hCG and an attempt of a fresh transfer is discouraged regardless of the number of oocytes collected (72.4% consensus). The choice of the FET protocol is not influenced by the fact that the patient is a hyper-responder (82.8% consensus). In the cases of freeze all due to OHSS risk, a FET cycle can be performed in the immediate first menstrual cycle (92.9% consensus). Conclusion: These guidelines for the management of hyper-response can be useful for tailoring patient care and for harmonizing future research. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Which patients might benefit from insemination of delayed-matured oocytes? SUMMARY ANSWER Delayed-matured oocytes had a ≥50% contribution to the available cohort of biopsied blastocysts in patients with advanced maternal age, low maturation, and/or low fertilization rates. WHAT IS KNOWN ALREADY Retrieved immature oocytes that progress to the MII stage in vitro could increase the number of embryos available during ICSI cycles. However, these delayed-matured oocytes are associated with lower fertilization rates and compromised embryo quality. Data on the ploidy of these embryos are controversial, but studies failed to compare euploidy rates of embryos derived from delayed-matured oocytes to patients' own immediate mature sibling oocytes. This strategy efficiently allows to identify the patient population that would benefit from this approach. STUDY DESIGN, SIZE, DURATION This observational study was performed between January 2019 and June 2021 including a total of 5449 cumulus oocytes complexes from 469 ovarian stimulation cycles, from which 3455 inseminated matured oocytes from ICSI (n = 2911) and IVF (n = 544) were considered as the sibling controls (MII-D0) to the delayed-matured oocytes (MII-D1) (n = 910). Euploidy rates were assessed between delayed-matured (MII-D1) and mature sibling oocytes (MII-D0) in relation to patients' clinical characteristics such as BMI, AMH, age, sperm origin, and the laboratory outcomes, maturation, fertilization, and blastocyst utilization rates. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 390 patients undergoing IVF/ICSI, who had at least one metaphase I (MI) or germinal-vesicle (GV) oocyte on the day of oocyte collection (Day 0), which matured in 20–28 h after denudation were included. MI and GV oocytes that matured overnight were inseminated on the following day (Day 1, MII-D1) by ICSI. Only cycles planned for preimplantation genetic testing for aneuploidy using fresh own oocytes were included. MAIN RESULTS AND THE ROLE OF CHANCE Fertilization (FR) and blastocyst utilization rates were significantly higher for MII-D0 compared to delayed-matured oocytes (MII-D1) (69.5% versus 55.9%, P  < 0.001; and 59.5% versus 18.5%, P  < 0.001, respectively). However, no significant difference was observed in the rate of euploid embryos between MII-D0 and MII-D1 (46.3% versus 39.0%, P  = 0.163). For evaluation of the benefit of inseminating MI/GV oocytes on D1 per cycle in relation to the total number of biopsied embryos, cycles were split into three groups based on the proportion of MII-D1 embryos that were biopsied in that cycle (0%, 1–50%, and ≥50%). The results demonstrate that patients who had ≥50% contribution of delayed-matured oocytes to the available cohort of biopsied embryos were those of advanced maternal age (mean age 37.7 years), <10 oocytes retrieved presenting <34% maturation rate, and <60% fertilization rate. Every MII oocyte injected next day significantly increased the chances of obtaining a euploid embryo [odds ratio (OR) = 1.83, CI: 1.50–2.24, P  < 0.001] among MII-D1. The odds of enhanced euploidy were slightly higher among the MII-D1-GV matured group (OR = 1.78, CI: 1.42–2.22, P  < 0.001) than the MII-D1-MI matured group (OR = 1.54, CI: 1.25–1.89, P  < 0.001). Inseminating at least eight MII-D1 would have >50% probability of getting a euploid embryo among the MII-D1 group. LIMITATIONS, REASONS FOR CAUTION ICSI of MII-D1 was performed with the fresh or frozen ejaculates or testicular samples from the previous day. The exact timing of polar body extrusion of delayed-matured MI/GV was not identified. Furthermore, the time point of the final oocyte maturation to MII for the immature oocytes and for the oocytes inseminated by IVF could not be identified. WIDER IMPLICATIONS OF THE FINDINGS The results of this study might provide guidance to the IVF laboratories for targeting the patient's population who would benefit from MII-D1 ICSI without adhering to unnecessary costs and workload. STUDY FUNDING/COMPETING INTEREST(S) No external funding was received for this study. There are no conflicts of interest to be declared for any of the authors. There are no patents, products in development, or marketed products to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to investigate whether women with diminished ovarian reserve who planned for PGT-A exhibit a lower number of blastocysts for biopsy, ploidy outcomes, and blastocyst quality on day 5, regardless of age. Methods: A retrospective analysis was performed between March 2017 and July 2020 at ART Fertility Clinics Abu Dhabi, including couples that were triggered for final oocyte maturation in an ovarian stimulated cycle planned for PGT-A. Patients were stratified into four AMH groups: < 0.65 ng/ml, 0.65–1.29 ng/ml, 1.3–6.25 ng/ml, and > 6.25 ng/ml; four age categories: ≤ 30, 31–35, 36–40, and > 40 years. Main results and the role of chance: A total of 1410 couples with a mean maternal age of 35.2 ± 6.4 years and AMH of 2.7 ± 2.6 ng/ml were included. In a multivariate logistic regression analysis, controlling for age, the chance of having at least one blastocyst biopsied/stimulated cycle (1156/1410), the chance of having at least one euploid blastocyst/stimulated cycle (880/1410), and the chance of having one euploid blastocyst once biopsy was performed (880/1156) were affected in all patients with AMH < 0.65 ng/ml [AdjOR 0.18[0.11–0.31] p = 0.008)], [AdjOR 0.18 [0.11–0.29] p < 0.001], and [AdjOR 0.34 [0.19–0.61] p = 0.015] as well as in patients with AMH 0.65–1.29 ng/ml (AdjOR 0.52 [0.32–0.84] p < 0.001), (AdjOR 0.49 [0.33–0.72] p < 0.001), and (AdjOR 0.57 [0.36–0.90] p < 0.001), respectively. In a multivariate linear regression analysis, AMH values did not affect blastocyst quality (− 0.72 [− 1.03 to − 0.41] p < 0.001). Conclusion: Irrespective of age, patients with diminished ovarian reserve (AMH < 1.3 ng/ml) have a lower chance of having at least one blastocyst biopsied and lower chance of having at least one euploid blastocyst per ovarian stimulated cycle. Blastocyst quality was not affected by AMH values. [ABSTRACT FROM AUTHOR]

Background: Studies have suggested that controlled ovarian hyperstimulation adversely affects endometrial receptivity due to advanced endometrial maturation. This adverse effect is mainly attributed to supraphysiological levels of both estrogen and progesterone identified in stimulated cycles. There is a paucity of published data investigating the very early luteal steroid profile following hCG trigger. Aim of the study: This prospective, observational study was undertaken to determine the increase in serum progesterone levels after human chorionic gonadotrophin (hCG) trigger in stimulated IVF/ICSI cycles. Materials and methods: This proof-of-concept study included 11 patients requiring ovarian stimulation for IVF/ICSI and who planned to avail of pre-implantation genetic screening with embryo vitrification of their biopsied embryos at blastocyst stage. For each study participant, five additional blood samples were drawn at the following specific times in the stimulation cycle, on the morning (10.00–12.00) of the assigned day to induce final oocyte maturation with hCG trigger, immediately prior to administration of hCG for final oocyte maturation, 1 h, 2 h, and 36 h post hCG trigger. A prediction model, the Gompertz curve, was used to determine serum progesterone levels at intervals between the 2 h post hCG trigger sample and the day of oocyte retrieval. Results: Statistically significant increases in serum progesterone levels were identified following hCG administration as early as 1 h following trigger (P4 0.57 ng/ml, p < 0.05), 2 h following trigger (P4 0.88 ng/ml, p < 0.001) and on the day of oocyte retrieval (P4 9.68 ng/ml, p < 0.001). According to our prediction model, the Gompertz curve, the projected serum progesterone level at 4 h post trigger would have achieved a level of 1.45 ng/ml, 8 h post trigger of 3.04 ng/ml, and 12 h post trigger of 4.8 ng/ml. The very early and significant increases in serum progesterone following hCG trigger are clearly demonstrated in this study. Conclusion: The endometrium is undoubtedly exposed to rapidly increasing serum progesterone levels post hCG trigger that would not be identified until much later in natural menstrual cycles. Trial registration number: This study is registered with clinicaltrials.gov under the identifier NCT04417569. [ABSTRACT FROM AUTHOR]

The purpose of this pilot study was to compare the endocrinological environment of cycles stimulated with clomiphene citrate (CC) or letrozole. Fifteen patients undergoing intrauterine insemination (IUI) received from day 3 to day 7 of the cycle either letrozole 2.5 mg/day (n = 7) or clomiphene citrate 100 mg/day (n = 8). IUI was performed one day after the detection of LH peak. No luteal support was administered. Significantly lower serum oestradiol concentrations were present in the follicular phase on days 9, 13 and 15 of the cycle and in the luteal phase on days 3 and 6 post-IUI in the letrozole group compared with those in the CC group. Progesterone concentrations and oestradiol concentrations were significantly lower in the letrozole group than in the CC group on the day of LH peak. Significantly more follicles developed in patients in the CC group compared with those in the letrozole group. In conclusion, significantly lower oestradiol concentrations and fewer follicles are observed in cycles stimulated with 2.5 mg letrozole compared with cycles stimulated with 100 mg CC from day 3 to day 7 of the cycle. [ABSTRACT FROM AUTHOR]

This article discusses the assessment of interindividual follicular size variation at ovulation in natural-cycle frozen embryo transfer (FET). The study found that there is considerable variation in follicular size at ovulation, ranging from 12 to 26 mm. The authors suggest that relying solely on parameters such as follicle size, estradiol (E2) level, and cycle day may be unreliable for establishing monitoring intervals and predicting ovulation in the first natural-cycle FET. They propose that measuring progesterone (P4) levels could be used to confirm ovulation and plan embryo transfer, reducing the costs of hormonal monitoring. [Extracted from the article]

Is female age a significant factor in the likelihood of an ongoing pregnancy in single euploid frozen embryo transfers (FET)? Retrospective study of 1923 single euploid FET cycles in 1464 women, either in a natural cycle or a hormone replacement therapy cycle. The primary outcome was the ongoing pregnancy rate (OPR). There were 990 (51.48%) ongoing pregnancies among 1923 included transfers. The OPR were 51.4%, 49.1%, 53.3% and 52.3% for women aged ≤35, >35–≤37, >37–≤40 and >40 years at oocyte retrieval (OCR), without a significant trend for decreasing OPR (P = 0.679). No significant differences in female age at embryo transfer (P = 0.609) and female age at OCR (P = 0.816) were found between the groups (ongoing pregnancy versus no pregnancy or miscarriage). Women who received good-quality embryos (P < 0.001), had a lower body mass index (BMI) (P < 0.001), had achieved at least one pregnancy previously (P < 0.001), and underwent natural cycle endometrial preparation (P < 0.001) were more likely to achieve an ongoing pregnancy. Multivariable regression analysis (adjusted for BMI, embryo quality and endometrial preparation) did not show a significant effect of female age at OCR on achieving an ongoing pregnancy. Compared with women aged ≤35 years, none of the age groups had significantly higher or lower OPR. A multinomial regression analysis showed that BMI, embryo quality and endometrial preparation were associated with miscarriage/no pregnancy versus ongoing pregnancy (P = 0.001, 0.001 and 0.001, respectively). Female age had no significant association with either outcome. Female age in itself does not have a substantial impact on the OPR in single euploid FET cycles, but the OPR is impacted significantly by embryo quality, BMI, previous parity, and a natural cycle endometrial preparation protocol. [ABSTRACT FROM AUTHOR]

• Anti-Müllerian hormone (AMH) is a reliable predictor of the superovulation capacity in dromedary camels. • Circulating AMH concentrations are highly repeatable in each individual camel. • Embryo donors can be categorized more subjectively by AMH measurement into high and low responders. Anti-Müllerian hormone (AMH) has a conserved role in regulating the reproductive cycle in several species. Its circulating concentration reflects the size of the growing primordial follicle reserve and is a reliable predictor of superovulation response in embryo/oocyte donors. This study investigated the possible application of AMH measurement in dromedary camels (Camelus dromedarius) multiple ovulation embryo transfer programs. In experiment 1, the follicular cycle of synchronized and naturally cycling camels (n = 12) was monitored. Blood was collected at 6 timepoints in 2 consecutive cycles corresponding to emergence, mid-cycle, and dominance in both group and hormonal fluctuations were evaluated for repeatability of measurements within and between cycles. In experiment 2, the correlation between circulating AMH concentrations prior to initiation of superovulation and the outcome of superovulation was evaluated. The results were compared between donors with higher (n = 7) and lower than median (n = 8) AMH values. Mean AMH concentrations in synchronized and non-synchronized camels were 1.46 ± 0.15 and 0.95 ± 0.09, respectively. Intercycle and intracycle values of AMH showed high repeatability in camels of both groups (>96.4% and >92.74%, respectively) with significant correlations between values at different stages of the ovarian cycle (Emergence and mid-cycle: R2 = 0.82; emergence and. dominance: R2 = 0.86; Mid-cycle and dominance: R2 = 0.93, P < 0.05). Total follicles, CLs, and recovered embryos were highly correlated with AMH values prior to superovulation (R2 = 0.64, R2 = 0.77, and R2 = 0.64, respectively, P < 0.05). A greater number of developed follicles prior to mating (17.00 ± 2.09 vs. 7.62 ± 1.06), CLs (12.58 ± 1.36 vs. 5.12 ± 0.93), transferable (10.85 ± 1,31 vs. 3.37 ± 0.82), and spherical embryos (8.14 ± 1.07 vs. 2.62 ± 0.7) were observed in camels with higher than median concentrations of AMH (P < 0.05). Fluctuations in estradiol and progesterone did not affect variations in mean AMH values (r2 < 0.19 and r2 < 0.24, respectively, P > 0.05). In conclusion, highly consistent AMH values in dromedary camels are a reliable predictor of superovulation response and outcome in dromedary camels. [ABSTRACT FROM AUTHOR]

There is an ongoing debate regarding the impact of premature progesterone rise on the IVF outcome. The objective of this review is to assess evidence of poorer ongoing pregnancy rate in IVF cycles with elevated serum progesterone at the end of follicular phase in ovarian stimulation. It also explores the origin of the progesterone rise, potential modifying factors and possible methods to prevent its rise during ovarian stimulation. This review draws on information already published from monitoring progesterone concentrations at the end of follicular phase in ovarian stimulation. The databases of Medline and PubMed were searched to identify relevant publications. Good-quality evidence supports the negative impact on endometrial receptivity of elevated progesterone concentrations at the end of the follicular phase in ovarian stimulation. Future trials should document the cause and origin of premature progesterone in stimulated IVF cycles. [ABSTRACT FROM AUTHOR]