Predicting live birth for poor ovarian responders: the PROsPeR concept

Lehert, Philippe; Chin, Wai; Schertz, Joan; D’Hooghe, Thomas; Alviggi, Carlo; Humaıdan, Peter

doi:10.1016/j.rbmo.2018.03.013

Cited by 17 publications

(7 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There were no differences observed in efficacy outcomes (number of oocytes retrieved [primary endpoint]; biochemical pregnancy rate, CPR, OPR; and LBR) between patients receiving r-hFSH/r-hLH and those receiving r-hFSH alone. However, a post-hoc analysis of the ESPART study observed a higher live birth rate with r-hLH supplementation in patients with moderate or severe POR, while a higher live birth rate was observed with r-hFSH alone in patients with mild POR (130).…”

Section: Recombinant Gonadotropinsmentioning

confidence: 99%

The Development of Gonadotropins for Clinical Use in the Treatment of Infertility

et al. 2019

Self Cite

View full text Add to dashboard Cite

The first commercially available gonadotropin product was a human chorionic gonadotropin (hCG) extract, followed by animal pituitary gonadotropin extracts. These extracts were effective, leading to the introduction of the two-step protocol, which involved ovarian stimulation using animal gonadotropins followed by ovulation triggering using hCG. However, ovarian response to animal gonadotropins was maintained for only a short period of time due to immune recognition. This prompted the development of human pituitary gonadotropins; however, supply problems, the risk for Creutzfeld–Jakob disease, and the advent of recombinant technology eventually led to the withdrawal of human pituitary gonadotropin from the market. Urinary human menopausal gonadotropin (hMG) preparations were also produced, with subsequent improvements in purification techniques enabling development of products with standardized proportions of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activity. In 1962 the first reported pregnancy following ovulation stimulation with hMG and ovulation induction with hCG was described, and this product was later established as part of the standard protocol for ART. Improvements in immunopurification techniques enabled the removal of LH from hMG preparations; however, unidentified urinary protein contaminants remained a problem. Subsequently, monoclonal FSH antibodies were used to produce a highly purified FSH preparation containing <0.1 IU of LH activity and <5% unidentified urinary proteins, enabling the formulation of smaller injection volumes that could be administered subcutaneously rather than intramuscularly. Ongoing issues with gonadotropins derived from urine donations, including batch-to-batch variability and a finite donor supply, were overcome by the development of recombinant gonadotropin products. The first recombinant human FSH molecules received marketing approvals in 1995 (follitropin alfa) and 1996 (follitropin beta). These had superior purity and a more homogenous glycosylation pattern compared with urinary or pituitary FSH. Subsequently recombinant versions of LH and hCG have been developed, and biosimilar versions of follitropin alfa have received marketing authorization. More recent developments include a recombinant FSH produced using a human cell line, and a long-acting FSH preparation. These state of the art products are administered subcutaneously via pen injection devices.

show abstract

Section: Recombinant Gonadotropinsmentioning

confidence: 99%

The Development of Gonadotropins for Clinical Use in the Treatment of Infertility

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, the ESHRE Bologna criteria do not aim to differentiate between oocyte quality and oocyte quantity; instead aiming to identify a homogenous population with reduced ovarian reserve, rather than a population with similar prognoses for pregnancy [41]. Despite these shortcomings, we propose that poor responders are defined according to the Bologna criteria, as analyses suggest they are clinically relevant [43]. Therefore, poor responders are patients from whom we would expect to retrieve 3 oocytes after conventional COS.…”

Section: Ovulatory Women (Including Women With Unexplained Infertilitmentioning

confidence: 99%

“…The aim of these tools is to provide an objective recommendation for embryologists, enabling the standardization of treatment across different centers by removing operator variability/subjectivity. This is an important goal, as center effect and operator variability are major contributors to differences in treatment outcomes for fertility treatment [43,71]. These tools are being designed to work together with the automation of key steps in the embryo lab (e.g.…”

Section: Future Perspectivesmentioning

confidence: 99%

Decision points for individualized hormonal stimulation with recombinant gonadotropins for treatment of women with infertility

Lunenfeld

Bilger

Longobardi

et al. 2019

Gynecological Endocrinology

View full text Add to dashboard Cite

It is essential that fertility treatment is individualized based on a thorough diagnostic work-up, with treatment tailored to the patients' requirements. This individualization should be kept in mind during the main decision points that occur before and during treatment. Treatment customization must include consideration of both the woman and her partner involved in the process together, including their collective treatment goals. Once treatment goals have been agreed and diagnostic evaluations performed, personalization based on patient characteristics, together with an understanding of treatment goals and patient preferences, enables the selection of appropriate treatments, protocols, products and their dosing. Following treatment initiation, monitoring and adaptation of product and dose can then ensure optimal outcomes. Currently, it is not possible to base treatment decisions on every characteristic of the patient and personalization is based on biomarkers that have been identified as the most relevant. However, in the future, the use of artificial intelligence coupled with continuous monitoring should enable greater individualization and improve outcomes. This review considers the current state-of-the-art related to decision points during individualized treatment of female infertility, before looking at future developments that might further assist in making individualized treatment decisions, including the use of computer-assisted decision making. ARTICLE HISTORY

show abstract

“…As women are increasingly deferring family building into more advanced reproductive ages, with the associated compromised ovarian reserve, correct predictions of pregnancy chances become even more important in counseling patients with a more unfavorable prognosis ( Lehert et al , 2018 ). Our academically affiliated fertility center serves a population of infertile women with a very high prevalence of diminished ovarian reserve (DOR), mostly related to advanced female age or premature ovarian aging (POA) ( Gleicher et al , 2015 ).…”

Section: Introductionmentioning

confidence: 99%

The ovarian sensitivity index is predictive of live birth chances after IVF in infertile patients

Weghofer

Barad

Darmon

et al. 2020

Human Reproduction Open

View full text Add to dashboard Cite

STUDY QUESTION Does the ovarian sensitivity index (OSI) predict embryo quality, pregnancy and live birth in patients undergoing FSH/hMG stimulation for IVF? SUMMARY ANSWER The OSI is predictive of pregnancy and live birth in older women with a more unfavorable prognosis undergoing FSH/hMG stimulation for IVF. WHAT IS KNOWN ALREADY The OSI was previously reported to reflect gonadotrophin requirements among high, normal and poor responders and to predict pregnancy potential in younger patients undergoing ovarian stimulation with FSH. STUDY DESIGN, SIZE, DURATION A retrospective cohort study that included 1282 women undergoing IVF with FSH/hMG stimulation was carried out between January 2010 and December 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS We evaluated 1282 women who underwent fertility treatment with FSH/hMG stimulation and oocyte retrieval at an academically affiliated private fertility center. OSI was calculated as (oocytes ×1000)/total gonadotrophin dose and grouped into two classes based on a receiver operating characteristic (ROC) curve analysis of a randomly selected development sample comprising one-third of the cycles. The remaining cycles comprised the validation group. ROC curves were also used to compare the predictive value of OSI to that of baseline FSH and anti-Müllerian hormone (AMH). Logistic regression models evaluated the effect of high (OSI >0.83) and low (OSI ≤0.83) on clinical pregnancy and live birth in the validation group. Models were adjusted for female age, baseline FSH, AMH and oocyte yield and gonadotrophin dose. MAIN RESULTS AND THE ROLE OF CHANCE Women presented with a mean ±SD age of 38.6 ± 5.4 years and showed median AMH levels of 0.65 (95% CI 0.61–0.74) ng/ml. They received 5145 ± 2477 IU of gonadotrophins and produced a median 5.2 (95% CI 5.0–5.5) oocytes. Pregnancy and live birth rates per oocyte retrieval for all women were 20.6% and 15.8%, respectively. Patients with higher OSI (less gonadotrophin required per oocyte retrieved) produced significantly more high-quality embryos than patients with low OSI (3.5 (95% CI 3.2–3.8) versus 0.6 (95% CI 0.5–0.7) (P = 0.0001)) and demonstrated higher pregnancy (23.2% versus 9.7%) and live birth rates (8.8% versus 5.3%) than their counterparts (P = 0.0001 and P = 0.0001, respectively). After adjustments for age, baseline AMH and FSH, total gonadotrophin dosage and oocyte yield, an OSI >0.83 was associated with greater odds of pregnancy (odds ratio 2.12, 95% CI 1.30–3.45, P < 0.003) and live birth (odds ratio 1.91, 95% CI 1.07–3.41, P < 0.028). LIMITATIONS, REASONS FOR CAUTION The results may not be applicable to women with excellent pregnancy potential or FSH-only stimulation. WIDER IMPLICATIONS OF THE FINDINGS The predictive capacity of OSI for embryo quality, pregnancy and live birth, which is independent of AMH or FSH, may help in counseling patients about their pregnancy potential and live birth chances. STUDY FUNDING/COMPETING INTEREST(S) Intramural funding from the Center for Human Reproduction and the Foundation for Reproductive Medicine. A.W., V.A.K., D.F.A., D.H.B. and N.G. have received research grant support, travel funds and speaker honoraria from various pharmaceutical and medical device companies: none, however, related to the topic presented here. D.H.B. and N.G. are listed as inventors on already awarded and still pending US patents, claiming beneficial effects on diminished ovarian reserve and embryo ploidy from dehydroepiandrosterone supplementation. TRIAL REGISTRATION NUMBER N/A.

show abstract

Predicting live birth for poor ovarian responders: the PROsPeR concept

Abstract: This model, specific to PORs receiving r-hFSH, constitutes the best compromise between precision and simplicity, and is suitable for routine practice.

Cited by 17 publications

References 43 publications

The Development of Gonadotropins for Clinical Use in the Treatment of Infertility

The Development of Gonadotropins for Clinical Use in the Treatment of Infertility

Decision points for individualized hormonal stimulation with recombinant gonadotropins for treatment of women with infertility

The ovarian sensitivity index is predictive of live birth chances after IVF in infertile patients

Contact Info

Product

Resources

About