Ovarian GnRH Research Articles

P-583 The ploidy status in blastocysts generated from progestin primed ovarian stimulation and GnRH antagonist protocols: A comparison of 14.000 trophectoderm biopsies

Abstract Study question Is there any difference in the euploidy rate in a large cohort of blastocysts when produced after a progestin-primed or GnRH antagonist protocol? Summary answer Euploidy rates in trophectoderm biopsies when tested with next-generation sequencing (NGS) were similar after progestin-primed or GnRH antagonist protocol. What is known already Preimplantation genetic testing (PGT) might be employed in patients with advanced female age to improve efficiency of embryo transfer. Given the fact that there is no fresh embryo transfer in that policy, progestin primed ovarian stimulation (PPOS) protocol might be preferred over GnRH analogs due to its lower cost and advantage of oral administration instead of s.c injections. However, due to small sample sizes within the limited number of studies, there is lack of consensus whether ploidy status might be affected when an embryo is generated after a PPOS or GnRH analogs protocol. Study design, size, duration A retrospective cohort study was designed among patients that has undergone in-vitro fertilization (IVF) treatment between January-2018 and June-2023 in Bahceci Health Group. For the aim of PGT, only patients treated with PPOS or GnRH antagonists were included. PPOS protocol referred to utilization of either medroxyprogesterone acetate (10 mg/day) or dydrogesterone (20-30 mg/day) to avoid premature ovulation during ovarian stimulation. In GnRH antagonist protocol, flexible or fixed approach was preferred for pituitary suppression. Participants/materials, setting, methods During the study period, 11.616 and 2.480 trophectoderm biopsies had been performed from blastocysts (D5/6) generated after GnRH antagonist or PPOS protocol, respectively. Of them, 9.390 and 1.801 of them were analyzed with NGS. A total of 303 (3.2%) and 17 (0.9%) biopsies were excluded due to failure or non-informative results after testing. For the final analysis, 9.087 and 1.784 biopsies were included in the antagonist and PPOS arms for the current study. Main results and the role of chance The mean age of women treated with GnRH antagonist and PPOS was comparable (36.5±5.3 vs. 36.7±5.4 years, p = 0.17). The respective numbers of euploid embryos were 3.912 and 1.784. Per biopsied embryos, the rate of euploidy was 33.7% and 34.8% (p = 0.30). The rate of euploidy per metaphase II oocyte and 2-PN were 10.6% and 13.5% in the GnRH antagonist arm and they were 11.3% and 14.4% in the PPOS arm (p = 0.08 and p = 0.07) without any statistical significance. When only patients included in whom all available blastocysts were biopsied, the linear regression model revealed only female age (RR: -0.32 CI%95: -0.38 to – 0.26, p < 0.001) as the independent factor for the prediction of ploidy rate (euploid/euploid + aneuploid embryos) when body mass index, duration of infertility, AMH, number of oocytes, number of metaphase-II oocytes, and the type of ovarian stimulation protocol were entered into the model. This model represented female age as the sole independent factor (RR: -0.14 CI%95: -0.18 to – 0.11, p < 0.001) when euploidy rate per 2PN was tested with the same variables. Limitations, reasons for caution The inherent risks cannot be excluded due to the retrospective nature of the current study. Wider implications of the findings The current study includes the largest number of trophectoderm biopsies generated from PPOS and GnRH antagonist protocol, giving the opportunity to compare them with each other. Due to lack of any superiority of one protocol regarding ploidy status, financial cost and easiness might favor PPOS when PGT is planned. Trial registration number None

Comparison of aneuploidy for patients of different ages treated with progestin-primed ovarian stimulation or GnRH antagonist protocols

Does euploidy status differ among patients of different ages treated with progestin-primed ovarian stimulation (PPOS) or gonadotrophin releasing hormone antagonist (GnRH-a) protocols? Patients undergoing PGT-A (n = 418; 440 cycles) were enrolled and grouped according to female age (<35 years and ≥35 years). Protocols were as follows: PPOS: <35 years (n = 131; 137 cycles); ≥35 years (n = 72; 80 cycles); GnRH-a: <35 years (n = 149; 152 cycles); ≥35 years (n = 66; 71 cycles). For cycles treated with PPOS in the older group, rates of euploid blastocyst per metaphase Ⅱ oocyte (15.48% versus 10.47%) and per biopsied blastocyst (54.94% versus 40.88%) were significantly higher than those treated with GnRH-a (P < 0.05). The mosaic rate per biopsied blastocyst was significantly lower for cycles treated with PPOS than cycles treated with GnRH-a (8.64% versus 23.36%) (P < 0.001). In the younger group, no significant difference was found between treatments (P > 0.05). In older and younger groups, the drug to inhibit LH surge was cheaper for cycles treated with PPOS compared with GnRH-a (P < 0.001). Generalized estimation equations based on binomial distribution female age and euploidy rate was significantly negatively correlated for all participants (β -0.109, 95% CI -0.183 to -0.035, P = 0.004), and between GnRH-a protocol (reference: PPOS) and the euploidy rate in the older group (β -0.126, 95% CI -0.248 to -0.004, P = 0.042). Multiple logistic regression indicated that ovarian stimulation protocol was not associated with ongoing pregnancy rate (OR 0.652, 95% CI 0.358 to 1.177; P = 0.14). PPOS is suitable for patients undergoing PGT-A, particularly older patients for the higher euploid blastocyst rate attained by PPOS protocol.

Cellular localization and seasonal variation of GnRH and Bradykinin in the ovary of Heteropneustes fossilis (Bloch.) during its reproductive cycle

The present study investigates the distribution and dynamics of gonadotropin-releasing hormone I (GnRH I) and bradykinin in the air-breathing catfish, Heteropneustes fossilis, in relation to the reproductive cycle. Changes in bradykinin, bradykinin B2-receptor, and ovarian GnRH I regulation were demonstrated during the reproductive cycle. The localization of GnRH I, bradykinin, and their respective receptors in the ovaries was investigated by immunohistochemistry, while their levels were quantified by slot/western blot followed by densitometry. GnRH I and its receptor were mainly localized in the cytoplasm of oocytes during the early previtellogenic phase. However, as the follicles grew larger, immunoreactivity was observed in the granulosa and theca cells of the late previtellogenic follicles. The ovaries showed significantly higher expression of GnRH I protein and its receptor during the early to mid-previtellogenic phase, suggesting their involvement in follicular development. Bradykinin and bradykinin B2-receptor showed a distribution pattern similar to that of GnRH I and its receptor. This study further suggested the possibility that bradykinin regulates GnRH I synthesis in the ovary. Thus, we show that the catfish ovary has a GnRH-bradykinin system and plays a role in follicular development and oocyte maturation in H. fossilis.

Ovarian response and embryo ploidy following oral micronized progesterone-primed ovarian stimulation versus GnRH antagonist protocol. A prospective study with repeated ovarian stimulation cycles.

Is there any difference in ovarian response and embryo ploidy following progesterone-primed ovarian stimulation (PPOS) using micronized progesterone or GnRH antagonist protocol? Pituitary downregulation with micronized progesterone as PPOS results in higher number of oocytes retrieved and a comparable number of euploid blastocysts to a GnRH antagonist protocol. Although the GnRH antagonist is considered by most the gold standard protocol for controlling the LH surge during ovarian stimulation (OS) for IVF/ICSI, PPOS protocols are being increasingly used in freeze-all protocols. Still, despite the promising results of PPOS protocols, an early randomized trial reported potentially lower live births in recipients of oocytes resulting following downregulation with medroxyprogesterone acetate as compared with a GnRH antagonist protocol. The scope of the current prospective study was to investigate whether PPOS with micronized progesterone results in an equivalent yield of euploid blastocysts to a GnRH antagonist protocol. In this prospective study, performed between September 2019 to January 2022, 44 women underwent two consecutive OS protocols within a period of 6 months in a GnRH antagonist protocol or in a PPOS protocol with oral micronized progesterone. Overall, 44 women underwent two OS cycles with an identical fixed dose of rFSH (225 or 300 IU) in both cycles. Downregulation in the first cycles was performed with the use of a flexible GnRH antagonist protocol (0.25 mg per day as soon as one follicle of 14 mm) and consecutively, after a washout period of 1 month, control of LH surge was performed with 200 mg of oral micronized progesterone from stimulation Day 1. After the completion of both cycles, all generated blastocysts underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuplody, PGT-A). Comparisons between protocols did not reveal differences between the duration of OS. The hormonal profile on the day of trigger revealed statistically significant differences between protocols in all the tested hormones except for FSH: with significantly higher serum E2 levels, more elevated LH levels and higher progesterone levels in PPOS cycles as compared with antagonist cycles, respectively. Compared with the GnRH antagonist protocol, the PPOS protocol resulted in a significantly higher number of oocytes (12.7 ± 8.09 versus 10.3 ± 5.84; difference between means [DBM] -2.4 [95% CI -4.1 to -0.73]), metaphase II (9.1 ± 6.12 versus 7.3 ± 4.15; DBM -1.8 [95% CI -3.1 to -0.43]), and 2 pronuclei (7.1 ± 4.99 versus 5.7 ± 3.35; DBM -1.5 [95% CI -2.6.1 to -0.32]), respectively. Nevertheless, no differences were observed regarding the mean number of blastocysts between the PPOS and GnRH antagonist protocols (2.9 ± 2.11 versus 2.8 ± 2.12; DBM -0.07 [95% CI -0.67 to 0.53]) and the mean number of biopsied blastocysts (2.9 ± 2.16 versus 2.9 ± 2.15; DBM -0.07 [95% CI -0.70 to 0.56]), respectively. Concerning the euploidy rates per biopsied embryo, a 29% [95% CI 21.8-38.1%] and a 35% [95% CI 26.6-43.9%] were noticed in the PPOS and antagonist groups, respectively. Finally, no difference was observed for the primary outcome, with a mean number of euploid embryos of 0.86 ± 0.90 versus 1.00 ± 1.12 for the comparison of PPOS versus GnRh antagonist. The study was powered to detect differences in the mean number of euploid embryos and not in terms of pregnancy outcomes. Additionally, per protocol, there was no randomization, the first cycle was always a GnRH antagonist cycle and the second a PPOS with 1 month of washout period in between. In case of a freeze-all protocol, clinicians may safely consider oral micronized progesterone to control the LH surge and patients could benefit from the advantages of a medication of oral administration, with a potentially higher number of oocytes retrieved at a lower cost, without any compromise in embryo ploidy rates. This research was supported by an unrestricted grant from Theramex. N.P.P. has received Research grants from Merck Serono, Organon, Ferring Pharmaceutical, Roche, Theramex, IBSA, Gedeon Richter, and Besins Healthcare; honoraria for lectures from: Merck Serono, Organon, Ferring Pharmaceuticals, Besins International, Roche Diagnostics, IBSA, Theramex, and Gedeon Richter; consulting fees from Merck Serono, Organon, Besins Healthcare, and IBSA. M.d.M.V., F.M., and I.R. declared no conflicts of interest. The study was registered at Clinical Trials Gov. (NCT04108039).

Efficacy of Progestin Primed Ovarian Stimulation versus GnRH Antagonist Protocols in Clomiphene Resistant PCOS Undergoing ICSI Cycles. Randomized Controlled Trial (RCT) aa

Efficacy of Progestin Primed Ovarian Stimulation versus GnRH Antagonist Protocols in Clomiphene Resistant PCOS Undergoing ICSI Cycles. Randomized Controlled Trial (RCT) aa

Expression of Concern: Laparoscopic ovarian drilling versus GnRH antagonist combined with cabergoline as a prophylaxis against the re-development of ovarian hyperstimulation syndrome

Expression of Concern: Laparoscopic ovarian drilling versus GnRH antagonist combined with cabergoline as a prophylaxis against the re-development of ovarian hyperstimulation syndrome

Non-inferiority of progestin-primed ovarian stimulation versus GnRH antagonist protocol: A propensity score-weighted analysis

PurposeTo evaluate the effectiveness of the progestin-primed ovarian stimulation (PPOS) protocol versus the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol in ovarian stimulation. MethodsIn this retrospective cohort study, we included 804 patients who were treated between January 1st, 2022, and July 1st, 2023. Outcomes of ovarian stimulation were compared between the PPOS (n = 206) and GnRH-ant (n = 598). The primary outcome was the number of good cleavage embryos. ResultsBaseline characteristics were comparable in both groups. In both unadjusted and adjusted analysis, the mean number of good cleavage embryos in PPOS (6.33) was non-inferior to GnRH-ant (6.44; unadjusted ratio of two means 1.02, 95%CI 0.92, 1.13). The trigger-day estradiol level in patients with PPOS was higher than in patients with GnRH-ant (4,420 vs 3,830 pg/ml, respectively) despite similar total follicle stimulating hormone dose and fewer days of ovarian stimulation. The number of oocytes, MII oocytes, cleavage and blastocyst embryos were comparable between the two protocols. After the first transfer of embryos, the clinical pregnancy rate and implantation rate were higher in the PPOS group, while the pregnancy rate and ongoing pregnancy were not significantly different. None of the PPOS patients had an unexpected LH surge, and serum LH levels decreased slightly during ovarian stimulation. ConclusionsThe PPOS protocol with dydrogesterone provided similar embryo outcomes to the GnRH-ant protocol, with notable distinctions in clinical pregnancy and implantation rate. The serum LH concentration during ovarian stimulation using PPOS was well-controlled.

Progestin-primed ovarian stimulation versus GnRH antagonist protocol in ICSI cycles in patients with different ovarian reserve: A retrospective cohort study

Progestin-primed ovarian stimulation versus GnRH antagonist protocol in ICSI cycles in patients with different ovarian reserve: A retrospective cohort study

Comparison of cumulative live birth rates between progestin-primed ovarian stimulation protocol and gonadotropin-releasing hormone antagonist protocol in different populations.

To compare cumulative live birth rate (LBR) between progestin-primed ovarian stimulation (PPOS) and GnRH antagonist protocols of preimplantation genetic testing (PGT) cycles in different populations. This was a retrospective cohort study. A total of 865 patients were enrolled and separate analyses were performed for three populations: 498 patients with predicted normal ovarian response (NOR), 285 patients with PCOS, and 82 patients with predicted poor ovarian response (POR). The primary outcome was cumulative LBR for one oocyte retrieval cycle. The results of response to ovarian stimulation were also investigated, including numbers of oocytes retrieved, MII oocytes, 2PN, blastocysts, good-quality blastocysts, and usable blastocysts after biopsy, as well as rates of oocyte yield, blastocyst formation, good-quality blastocysts, and moderate or severe OHSS. Univariable and multivariable logistic regression analyses were used to identify potential confounders that may be independently associated with cumulative live birth. In NOR, the cumulative LBR of PPOS protocol was significantly lower than that of GnRH antagonists (28.4% vs. 40.7%; P=0.004). In multivariable analysis, the PPOS protocol was negatively associated with cumulative LBR (adjusted OR=0.556; 95% CI, 0.377-0.822) compared to GnRH antagonists after adjusting for potential confounders. The number and ratio of good-quality blastocysts were significantly reduced in PPOS protocol compared to GnRH antagonists (2.82 ± 2.83 vs. 3.20 ± 2.79; P=0.032 and 63.9% vs. 68.5%; P=0.021), while numbers of oocytes, MII oocytes and 2PN did not show any significant difference between GnRH antagonist and PPOS protocols. PCOS patients had similar outcomes as NOR. The cumulative LBR of PPOS group appeared to be lower than that of GnRH antagonists (37.4% vs. 46.1%; P=0.151), but not significantly. Meanwhile, the proportion of good-quality blastocysts in PPOS protocol was also lower compared to GnRH antagonists (63.5% vs. 68.9%; P=0.014). In patients with POR, the cumulative LBR of PPOS protocol was comparable to that of GnRH antagonists (19.2% vs. 16.7%; P=0.772). There was no statistical difference in the number and rate of good-quality blastocysts between the two protocols in POR, while the proportion of good-quality blastocysts appeared to be higher in PPOS group compared to GnRH antagonists (66.7% vs. 56.3%; P=0.182). In addition, the number of usable blastocysts after biopsy was comparable between the two protocols in three populations. The cumulative LBR of PPOS protocol in PGT cycles is lower than that of GnRH antagonists in NOR. In patients with PCOS, the cumulative LBR of PPOS protocol appears to be lower than that of GnRH antagonists, albeit lacking statistical difference, whereas in patients with diminished ovarian reserve, the two protocols were comparable. Our findings suggest the need for caution when choosing PPOS protocol to achieve live births, especially for normal and high ovarian responders.

Comparable Pregnancy Loss and Neonatal Birthweights in Frozen Embryo Transfer Cycles Using Vitrified Embryos from Progestin-Primed Ovarian Stimulation and GnRH Analogue Protocols: A Retrospective Cohort Study.

Background: The potential correlation between progestin-primed ovarian stimulation (PPOS) and the risk of compromised embryo competence still lacks sound evidence. Methods: A large retrospective cohort study was used to compare the incidence of pregnancy loss and neonatal birthweights in frozen embryo transfer (FET) cycles using embryos from PPOS and GnRH analogue protocols. Propensity matched scores were used to balance the baseline confounders. Results: A total of 5744 matched cycles with positive hCG test were included to compare the pregnancy outcomes. The incidence of pregnancy loss was similar between PPOS and GnRH analogue groups (19.2% vs. 18.4%, RR 1.02 (0.97, 1.06), p > 0.05). The neonatal birthweights were comparable between two groups, respectively, for singleton births (3337.0 ± 494.4 g vs. 3346.0 ± 515.5 g) and in twin births (2496.8 ± 429.2 g vs. 2533.2 ± 424.2 g) (p > 0.05). Conclusions: The similar incidence of pregnancy loss and neonatal birthweights in FET cycles using embryos from PPOS provided us with a more complete picture about the safety of PPOS.

OPN5 Regulating Mechanism of Follicle Development Through the TSH-DIO2/DIO3 Pathway in Mountain Ducks Under Different Photoperiods.

: Photoperiod is an important environmental factor that influence seasonal reproduction behavior in bird. Birds translates photoperiodic information into neuroendocrine signals through deep brain photoreceptors (DBPs). OPN5 has been considered as candidate DBPs involving in regulation of seasonal reproduction in birds. However, little is known about the effect of OPN5 in non-seasonal breeding birds. Thus, we pondered on whether OPN5 regulating follicular development through TSH-DIO2/DIO3 system responds to different photoperiods in non-seasonal laying ducks. As an ideal non-seasonal breeding bird, a total of 120 mountain ducks were randomly divided into three groups and treated respectively to a different photoperiod: group S (8 L:16D), group C (17 L:7D), and group L (24 L:0D). The ducks were caged in a fully enclosed shelter with the same feeding conditions for each group, free water and limited feeding (150 g per duck each day). Samples were collected from each group at d 0, d 5, d 8, d 20, and d 35 (n = 8). The ducks in 24 h photoperiod had the highest laying rate and the lowest feed-to-egg ratio, while the ducks in 8 h photoperiod had the lowest laying rate and the highest feed-to-egg ratio. Long-day photoperiod for 24 h significantly increased the ovarian index and GnRH, LH, E2, and P4 levels in serum; short-day photoperiod for 8 h increased testosterone levels in serum. Compared with 8 h photoperiod, long-day photoperiod significantly or highly significantly increased the mRNA level and protein expression of OPN5 in the hypothalamus of long-day photoperiod on d 35 (p < 0.05). The gene or protein expression patterns of GnRH, TRH, TSHβ, DIO2, THRβ, VIP, and PRL were positively correlated with OPN5, whereas the gene expression patterns of GnIH and DI O 3 were negatively correlated with OPN5. The results revealed that OPN5 mediated the effect of light on follicular development through the TSH-DIO2/DIO3 pathway, the expression of OPN5 increased with light duration and improved the efficiency of the HPG axis to promote follicular development in mountain ducks.

Impact of Surgical Management of Endometrioma on Ovarian Reserve

Objective: The aim of this study was to explore the outcome of surgical removal of endometriotic cyst on ovarian reserve.&#x0D; Materials and methods: This prospective observational study was carried out in Infertility Care and Research Centre, Dhaka, Bangladesh between January 2011 and December 2018. One hundred and fifty-five patients, who had an ultrasonographic diagnosis of endometrioma measuring ³3 cm and underwent surgical excision due to subfertility were the candidates for this study. The exclusion criteria were a) previous ovarian cystectomy, b) removal of one ovary, c) irregular menstrual cycle, d) polycystic ovarian syndrome e) endocrine disorder, f) low AMH (&lt;1ng/ml), g) history of taking medication for endometriosis that could affect ovarian function, e.g., GnRH analogues or oral contraceptives during the 6 months preceding scheduled surgery. To investigate the effect of surgery on ovarian reserve, their FSH, E2 and AMH were measured before and after surgery. Tests were done before surgery and repeated after 3 months and 6 months of surgery. A value of &lt; 0.05 was considered significant.&#x0D; Results: Mean age of the patients was 31.72 ±2.77 years. The baseline FSH, E2 and AMH were within normal limit. In 63.88% of the cases the cysts were unilateral and 83.22% of the cases the size of the cysts were within 10 cm. To assess the change of ovarian reserve FSH, E2 and AMH were measured in 3 and 6 months after surgery. There was marked declining of AMH level from baseline to both 3 months and 6 months after surgery p is &lt;0.0001. There was no significant change of FSH and AMH between 3 months and 6 months after surgery.&#x0D; Conclusion: Cystectomy in ovarian endometrioma significantly reduces ovarian reserve, which is menifested by reduced level of AMH.&#x0D; Bangladesh J Obstet Gynaecol, 2020; Vol. 35(2): 96-101

Association of the Serum Folate and Total Calcium and Magnesium Levels Before Ovarian Stimulation With Outcomes of Fresh In Vitro Fertilization Cycles in Normogonadotropic Women.

BackgroundWomen of reproductive age are recommended to consume folic acid and other supplements before conception and during pregnancy. We aimed to investigate the association of the serum folate and total magnesium (Mg) and calcium (Ca) levels before ovarian stimulation with the outcomes of assisted reproductive technology (ART) in normogonadotropic women.MethodsWe used a subanalysis of data obtained from a multicentre, randomized prospective study (NCT03088137). A total of 110 normogonadotropic, non-advanced aged, non-obese women with tubal and/or male infertility factors were enrolled for the single fresh ovarian stimulation GnRH antagonist cycle. The main outcome measures were the total oocyte yield, mature oocytes, fertilization rate, biochemical, clinical pregnancy, and live birth. Multivariable generalized linear models adjusted for covariates were used with a Poisson distribution and the log link function for adjusted oocyte counts, and a binomial distribution and the log link function were used for adjusted clinical ART outcomes.ResultsThe medians (interquartile range (IQR)) were as follows: baseline serum folate, 20.55 ng/ml (10.8, 32.9); Mg, 19.4 mg/L (18.7, 20.7); Ca, 94 mg/L (91.2, 96.4); and Ca/Mg ratio, 4.78 (4.55, 5.02). Women with higher serum folate concentrations (Q4≥33.0 ng/ml) had significantly lower total numbers of oocytes retrieved (adjusted mean (95% CI) 9.2 (7.6-11.3) vs 12.9 (10.9-15.4, p-trend=0.006)) and lower odds ratios (ORs) (95% CI) of 0.12 (0.02, 0.79) for clinical pregnancy and 0.10 (0.01, 0.70) for live birth compared with women in the lowest quartile (<10.8 ng/ml), all p-trend<0.001. Women in the highest Ca/Mg ratio quartile (≥5.02) had ORs (95% CI) of 6.58 (1.31, 33.04) for biochemical pregnancy, 4.85 (1.02, 23.08) for clinical pregnancy and 4.07 (0.83, 19.9) for the live birth rate compared with women in the lowest quartile (<4.55), all p-trend<0.001.ConclusionsUsing multivariable models, we suggested that a baseline elevated serum folate level (≥33.0 ng/ml) and a lower Ca/Mg ratio were associated with worse ART outcomes in normogonadotropic women. Our findings might be useful for choosing safe dosages of folate, calcium, magnesium and complex supplementation for both fertile women and women undergoing infertility treatment. Further preconception large-scale studies with known micro- and macronutrient statuses of both parents and serum folate, Ca, Mg, and hormone levels, are needed.

243 Relationship Among Granulosa Cell Gnrh-i, -II, and Receptor Mrna Abundance and Follicular Fluid Steroid Hormone Concentrations of Bovine Antral Follicles at Specific Stages of Follicular Development

Abstract Transcript abundance of two forms of GnRH and its receptor have been characterized in bovine ovaries. The objective was to investigate the relationship of GnRH-1, GnRH-2, GnRH-R, intrafollicular estradiol (E2) and progesterone (P4) during follicular development. Ovaries were collected from beef cows at specific stages of follicular development [pre-selection (PRE, n = 9), post-selection (POST, n = 9), and post-selection 24h after luteal regression (PG, n = 9)]. The largest follicle per stage was aspirated to obtain granulosa cells (GC) and follicular fluid (FF). Total cellular RNA was extracted from GC and RT-PCR was performed for GnRH-1, GnRH-2, GnRH-R and GAPDH. Radioimmunoassays were performed to determine FF concentrations of E2 and P4. Data were analyzed using the MIXED and REG procedures in SAS. There was no difference (P ≥ 0.23) in mRNA abundance of GnRH-2, GnRH-R or FF concentrations of P4 across follicular stages. There was an effect of stage on FF E2 (PRE: 17,925±20,273, POST: 28,458±21,503, and PG: 252,616±21,503 pg/mL; P &amp;lt; 0.01). Stage affected GnRH-1 mRNA abundance (PRE: 2.28±0.55, POST: 0.92±0.55, and PG: 0.11±0.55; P = 0.03). There was no relationship of GnRH-1 and GnRH-2 mRNA abundance or effect of FF P4 on GnRH-R mRNA abundance (P ≥ 0.23). There was no effect of FF P4 on GnRH-1 mRNA abundance (P = 0.68). There was no effect of FF E2 on GnRH-2 mRNA abundance (P = 0.66). As FF E2 increased GnRH-R mRNA abundance tended to increase (P = 0.10;r2=0.13). As FF P4 concentrations increased GnRH-2 mRNA abundance tended to decrease (P = 0.09;r2=0.12). As FF E2 increased GnRH-1 mRNA abundance decreased (P = 0.02;r2=0.20). In conclusion, there were differences in peptide and receptor mRNA abundance of GnRH in relation to FF E2 and P4 at specific stages of follicular development. This is supportive of a regulatory relationship between ovarian GnRH and steroidogenesis. This work is supported by AFRI Grant No.2018-67016-27578 from USDA. USDA is an equal opportunity provider and employer.

CUMULATIVE LIVE BIRTH RATES BETWEEN GnRH-AGONIST AND GnRH-ANTAGONIST PROTOCOL IN ONE ART CYCLE WHEN ALL EMBRYOS TRANSFERRED : REAL-WORD DATA STUDY INCLUDING 17842 WOMEN FROM CHINA

To compare the cumulative live birth rate (CLBR) of the first ART cycle including all subsequent frozen-thaw cycles in different ovarian stimulation protocol GnRH-agonist long protocol or GnRH antagonist protocol and find the clinical implication for agent choice.

LOWER SERUM FSH LEVELS IN RESPONSE TO IV RECOMBINANT FSH IN OBESE WOMEN IS NOT EXPLAINED BY GNRH ANTAGONIST (CETRORELIX) PHARMACODYNAMICS

ART employs GnRH suppression and FSH stimulation to induce follicular development. Obese women are known to require higher FSH doses during ART as compared to normal weight (NW) women. It remains unclear whether this higher exogenous FSH requirement for ART is related to abnormal hypothalamic-pituitary dynamics, abnormal ovarian environment or GnRH antagonist or FSH pharmacodynamics/ pharmacokinetics.

Traitements immunosuppresseurs et préservation de la fertilité : indications et modalités pratiques

Fertility preservation is routinely performed in cancerology but less systematically used in the field of immune diseases, even though the use of gonadotoxic treatments in young patients may be required and even though the disease itself can alter fertility. This review aimed to clarify the indications and methods of fertility preservation in this context. Cyclophosphamide is the only immunosuppressive drug requiring fertility preservation in women. In men, fertility preservation should be proposed before treatment with cyclophosphamide, methotrexate, mycophenolate mofetil or mTOR inhibitors. Other factors inherent to the disease or the patient may alter fertility. Thus, screening for infertility and fertility preservation have to be implemented as much as possible to increase the chances of successful procreation in patients with immune disease. For women, the choice between the different preservation methods depends on the patient's age, disease activity, the time available before the start of treatment, the possibility of future pregnancy and the woman's and even couple's wishes. Before puberty, the only accepted method is cryopreservation of ovarian tissue. After puberty, the first-line method is the cryopreservation of mature oocytes. If the treatment has to be started in an emergency, if ovarian hyperstimulation/oocyte retrieval is contraindicated or if the patient refuses this option, cryopreservation of ovarian tissue or GnRH agonists could be proposed. For men, the accepted method is sperm cryopreservation. For prepubertal boys, the cryopreservation of spermatogonia after testicular biopsy is still experimental.

Laparoscopic ovarian drilling versus GnRH antagonist combined with cabergoline as a prophylaxis against the re-development of ovarian hyperstimulation syndrome

Objective: The aim of this work was to investigate the value of laparoscopic ovarian drilling (LOD) compared with GnRH antagonist flexible protocol combined with cabergoline (Cb), as a prophylaxis against the re-development of ovarian hyperstimulation syndrome (OHSS) in women with clomiphene citrate-resistant polycystic ovary disease (CCR-PCOD) who had severe OHSS before in a previous ICSI cycle. Study design: It is a prospective controlled study, where 250 CCR-PCOD women (n = 250) with a history of severe OHSS before, had been recruited for the study. LOD had been performed for 120 (n = 120) of the recruited women before ovarian induction, and considered as group A. GnRH antagonist (Cetrotide 0.25 mg) was added when a leading follicle reaches 14–16 mm combined with oral Cb in a dose 0.5 mg a day before hCG, and for 8 d for another 130 (n = 130) women, and considered as group B. Pregnancy was diagnosed with BhCG level ≥25 IU/L, ± 14 d after embryo transfer, followed with transvaginal ultrasound scanning (TVS) 2 weeks later to confirm intra-uterine pregnancy (IUP). Women were followed up weekly for 3 months for the possible development of any signs and symptoms of OHSS. Results: None of the participants in group A developed severe OHSS, and only six women (5%) developed mild to moderate OHSS. The incidence of severe OHSS was significantly higher (n = 3, 15%) in group B compared with group A (p < .001). Another (n = 17, 13.3%) women in group B developed mild to moderate OHSS. The probability of developing severe OHSS was also significantly higher in group B as well (p = .031). Pregnancy rate (PR) was significantly higher in group A more than group B (67% versus 39%, respectively), and all were single intrauterine pregnancies (IUP) and all developed after fresh embryo transfer (ET), compared with frozen embryo transfer (FET) which was performed in 42 cases in group B after postponing ET due to significantly severe OHSS developed. Conclusion: LOD could be considered a good prophylactic measure against OHSS, in addition to improving the total outcome of IVF cycles in women with CCR-PCOS.

Surgical ovarian ablation cost effective versus GnRH

Surgical ovarian ablation cost effective versus GnRH

Dramatic acceleration of reproductive aging, contraction of biochemical fecundity and healthspan-lifespan implications of opioid-induced endocrinopathy—FSH/LH ratio and other interrelationships

Whilst disturbances of female reproductive hormones and function are commonplace in opioid dependence, their pathophysiological interrelationships are not well understood. Hormonal levels in females were compared in 77 opioid dependent patients (ODP) and 148 medical controls (MC) including 205 and 364 repeat studies. Significant changes in FSH, LH, oestradiol, testosterone and SBG were noted including power functions with age. The FSH/LH was lower in ODP (P=0.0150) and the ratio inversion point occurred at 28.06±9.36v. 46.26±4.76years, implying a 58% reduction in fertility duration. FSH has been shown to induce ovarian failure and GnRH (controlling LH and FSH) has been shown to regulate longevity systemically. This implies that, far from being benign, these findings explicate the adverse experience of female compared to male ODP, exacerbate opioid-dependent aging amongst females, and informs the care of opioid dependent women, particularly relating to the choice, dose and duration of agonist or antagonist therapy.