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Purpose: To assess whether the GnRH-agonist or urinary-hCG ovulation triggers affect oocyte competence in a setting entailing vitrified-warmed euploid blastocyst transfer., Methods: Observational study (April 2013-July 2018) including 2104 patients (1015 and 1089 in the GnRH-a and u-hCG group, respectively) collecting ≥1 cumulus-oocyte-complex (COC) and undergoing ICSI with ejaculated sperm, blastocyst culture, trophectoderm biopsy, comprehensive-chromosome-testing, and vitrified-warmed transfers at a private clinic. The primary outcome measure was the euploid-blastocyst-rate per inseminated oocytes. The secondary outcome measure was the maturation-rate per COCs. Also, the live-birth-rate (LBR) per transfer and the cumulative-live-birth-delivery-rate (CLBdR) among completed cycles were investigated. All data were adjusted for confounders., Results: The generalized-linear-model adjusted for maternal age highlighted no difference in the mean euploid-blastocyst-rate per inseminated oocytes in either group. The LBR per transfer was similar: 44% (n=403/915) and 46% (n=280/608) in GnRH-a and hCG, respectively. On the other hand, a difference was reported regarding the CLBdR per oocyte retrieval among completed cycles, with 42% (n=374/898) and 25% (n=258/1034) in the GnRh-a and u-hCG groups, respectively. Nevertheless, this variance was due to a lower maternal age and higher number of inseminated oocytes in the GnRH-a group, and not imputable to the ovulation trigger itself (multivariate-OR=1.3, 95%CI: 0.9-1.6, adjusted p-value=0.1)., Conclusion: GnRH-a trigger is a valid alternative to u-hCG in freeze-all cycles, not only for patients at high risk for OHSS. Such strategy might increase the safety and flexibility of controlled-ovarian-stimulation with no impact on oocyte competence and IVF efficacy.

Proper ovarian stimulation regimens are crucial for any patient undergoing in-vitro fertilization (IVF). However, maximizing the oocyte yield in advanced maternal age patients with poor or suboptimal response is still a challenge. In fact, no standard treatment has been outlined yet to manage these women. Across the last years, an improved efficiency of the IVF units via blastocyst culture, vitrification and reliable embryo selection approaches paved the way to the investigation of novel unconventional stimulation protocols, like double stimulation in a single ovarian cycle (DuoStim). DuoStim, by conjugating follicular phase stimulation (FPS) and luteal phase stimulation (LPS) in the same ovarian cycle, allows to maximize the number of oocytes obtained in a short timeframe, a precious outcome when we aim at shortening time to pregnancy. In this regard, LPS seems to contribute to conventional stimulation with more oocytes with a comparable competence as FPS, retrieved per ovarian cycle. Although any stimulation protocol which exploits anovulatory waves of follicular growth needs a thorough investigation, no evidence has been produced to question the safety of DuoStim, which to date represents the most intriguing strategy to treat poor prognosis in IVF.

Objective: To study the relative role of female age and ovarian reserve, measured through serum antimüllerian hormone (AMH) in determining the rate and number of euploid blastocysts in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles., Design: Retrospective analysis of cycles performed in 2014-2015., Setting: Tertiary referral IVF center., Patient(s): A total of 578 infertile couples undergoing IVF/ICSI and preimplantation genetic screening (PGS) analysis., Interventions(s): All embryos were cultured and biopsied at the blastocyst stage. The method involved whole-genome amplification followed by array comparative genome hybridization. Serum AMH was measured by means of the modified Beckman Coulter AMH Gen II assay., Main Outcome Measures: The rate and number of euploid blastocysts and their correlation with ovarian reserve and response to stimulation., Result(s): The mean (±SD) age of patients was 37.6 ± 4.1 years, and the mean number of blastocysts per patient was 3.1 ± 2. The total number of blastocysts available to the analysis was 1,814, and 36% of them were euploid after PGS. Age and serum AMH were significantly and independently related to the rate of euploid blastocysts available for patients. As an effect of the cohort size, the number of mature oocytes positively affected the total number of euploid blastocysts per patient., Conclusion(s): A strong positive age-independent relationship between AMH level and the rate of euploid blastocysts was found. This confirms that the measurement of ovarian reserve by means of AMH has high relevance when counseling infertile patients., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Since gonadotropins are the fundamental hormones that control ovarian activity, genetic polymorphisms may alter gonadal responsiveness to glycoproteins; hence they are important regulators of hormone activity at the target level. The establishment of the pool of primordial follicles takes place during fetal life and is mainly under genetic control. Consequently, single nucleotide polymorphisms (SNPs) in gonadotropins and their receptors do not seem to be associated with any significant modification in the endowment of nongrowing follicles in the ovary. Indeed, the age at menopause, a biological characteristic strongly related to ovarian reserve, as well as markers of functional ovarian reserve such as anti-Müllerian hormone and antral follicle count, are not different in women with different genetic variants. Conversely, some polymorphisms in FSH receptor (FSHR) seem to be associated with modifications in ovarian activity. In particular, studies suggest that the Ser680 genotype for FSHR is a factor of relative resistance to FSH stimulation resulting in slightly higher FSH serum levels, thus leading to a prolonged duration of the menstrual cycle. Moreover, some FSHR gene polymorphisms show a positive association with ovarian response to exogenous gonadotropin administration, hence exhibiting some potential for a pharmacogenetic estimation of the FSH dosage in controlled ovarian stimulation. The study of SNPs of the FSHR gene is an interesting field of research that could provide us with new information about the way each woman responds to exogenous gonadotropin administration during ovulation induction., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To elaborate a nomogram based on markers of ovarian reserve for the calculation of the appropriate starting dose of follicle-stimulating hormone (FSH)., Design: Cohort study of infertile women., Setting: In vitro fertilisation (IVF) unit, University Hospital of Modena, Italy., Population: Women aged 18-40 years (n = 346) and undergoing their first IVF cycle., Methods: Serum FSH and anti-Müllerian hormone (AMH) measurement., Main Outcome Measures: Development of a model for the prediction of ovarian response to FSH., Results: A model based on age, AMH and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting FSH dose <225 IU in 55.1 and 25.9% of women younger and older than 35 years, respectively., Conclusions: In the present study we clearly demonstrated that the daily FSH dose may be calculated on the basis of a woman's age and two markers of ovarian reserve, namely AMH and FSH, with the first two vari;s (age and AMH) being the most significant predictors. The nomogram we developed seems easily applicable for clinicians during their daily clinical practice., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

Please cite this paper as: La Marca A, Papaleo E, Grisendi V, Argento C, Giulini S, Volpe A. Development of a nomogram based on markers of ovarian reserve for the individualisation of the follicle-stimulating hormone starting dose in in vitro fertilisation cycles. BJOG 2012;119:1171-1179. Objective To elaborate a nomogram based on markers of ovarian reserve for the calculation of the appropriate starting dose of follicle-stimulating hormone (FSH). Design Cohort study of infertile women. Setting In vitro fertilisation (IVF) unit, University Hospital of Modena, Italy. Population Women aged 18-40 years ( n = 346) and undergoing their first IVF cycle. Methods Serum FSH and anti-Müllerian hormone (AMH) measurement. Main outcome measures Development of a model for the prediction of ovarian response to FSH. Results A model based on age, AMH and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting FSH dose <225 IU in 55.1 and 25.9% of women younger and older than 35 years, respectively. Conclusions In the present study we clearly demonstrated that the daily FSH dose may be calculated on the basis of a woman's age and two markers of ovarian reserve, namely AMH and FSH, with the first two vari;s (age and AMH) being the most significant predictors. The nomogram we developed seems easily applicable for clinicians during their daily clinical practice. [ABSTRACT FROM AUTHOR]