Natural ovarian stimulation (NATOS): an innovative controlled ovarian hyperstimulation (COH) protocol that combines large oocyte availability and physiologic estrogenic environment

Abstract Background: Although serum basal follicle stimulating hormone (FSH) is widely used to evaluate the ovarian response, the necessity of levels of serum FSH during the controlled ovarian hyperstimulation (COH) is controversy. When the ovarian response to COH is suboptimal due to the insufficient dose of FSH, which is often adjusted in subsequent treatment accordingly, we could detect serum FSH levels and considering that exogenous FSH is inadequate to optimal FSH threshold. We, therefore, aim to evaluate the association between the ovarian response and the difference value of serum FSH concentration in the first five days of ovarian stimulation. Methods: In this retrospective single-center study, patients were enrolled for first IVF/ICSI during the period from August 2015 to December 2017. The COH only included gonadotrophin-releasing hormone agonist (GnRH-a) protocols in which endogenous serum FSH values were suppressed, and stimulated with 150IU fixed-dose recombinant FSH (rFSH) during the first five days. Patients met all inclusion criteria were selected: age ≤ 40 years, body mass index (BMI) ≤ 32 kg/m2, regular menstruation cycle of 21-35 days and non-ovarian factor infertility. Groups were divided by the amount of oocytes collection as follows: (A) poor responders (n=27), (B) normal responders (n=638), (C) hyper responders (n=205). A multivariable logistic regression model was performed to evaluate the relationship between the ovarian response and difference value of serum FSH levels during the first five days of ovarian stimulation.Result(s): The difference value of serum FSH level (ΔFSH) between the sixth day and the first day during ovarian stimulation was measured as the primary outcome. Mean serum ΔFSH levels between groups B and C were 7.45 and 6.87, which had significant differences (p=0.0259). ΔFSH was stratified in quartiles as below: (a) ΔFSH≤5.16, (b) ΔFSH 5.16-7.11, (c) 7.11-9.09, (d) ΔFSH˃9.09. After adjusted by potential confounding factors, there was no relationship exists between ΔFSH levels and ovarian response.Conclusion(s): There is no relevance between the ovarian response and ΔFSH in the 150 IU fixed dose rFSH treatment protocol during COH. Serum FSH might not be used as an effective predictor for ovarian response and reproduction potential in IVF/ICSI clinical practice.

Download Full-text

Influence of short-term ovarian stimulation on bone metabolism in women undergoing fertility treatment

Journal of Laboratory Medicine ◽

10.1515/labmed-2020-0117 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Anna Ritzinger ◽

Monika Schmidmayr ◽

Bernd Lesoine ◽

Vanadin Seifert-Klauss

Keyword(s):

Bone Resorption ◽

Bone Metabolism ◽

Ovarian Stimulation ◽

Luteal Phase ◽

Influencing Factor ◽

Controlled Ovarian Hyperstimulation ◽

Fertility Treatment ◽

Ovarian Hyperstimulation ◽

Short Term ◽

Down Regulation

Abstract Objectives Hormonal disturbances during menopause are an established influencing factor on bone health, but the role of controlled ovarian hyperstimulation for fertility treatment remains unclear. To evaluate the influence of ovarian stimulation on bone metabolism with particular regard to serum follicle-stimulating hormone (FSH) levels this prospective observational study was conducted. Methods A total of 71 women underwent controlled ovarian hyperstimulation with recombinant FSH (rFSH) or human menopausal gonadotropin (HMG) (FSH + LH) administered in individual doses, with gonadotropin-releasing hormone (GnRH) agonist down-regulation initiated in the luteal phase of the previous cycle. At four time points (start of down-regulation [T1], start of ovarian stimulation [T2], oocyte retrieval [T3] and luteal phase of the stimulation cycle [T4]), luteinizing hormone (LH), FSH, estradiol (E2), osteocalcin (OC), bone-specific alkaline phosphatase (BAP), as well as the bone resorption markers β-isomerized C-terminal telopeptide of type I collagen (β-CTX) and tartrate-resistant acid phosphatase (TRACP) were measured. Results The cyclic variations in FSH levels had a positive effect on the concentration profile of the bone resorption marker β-CTX (p=0.0001). Supraphysiologic estradiol levels showed a negative association with osteocalcin concentrations (p=0.017), and significantly lower OC and TRACP levels were observed at T4 compared to T1. By group comparison, women treated with rFSH presented with a higher bone turnover than the HMG group at the end of a stimulation cycle (T4). Conclusions Our results show that FSH is a significant influencing factor of bone metabolism. Overall, there was no evidence of enhanced bone resorption under short-term ovarian stimulation therapy. Further studies with bigger sample sizes are warranted to validate these results.

Download Full-text

Controlled ovarian hyperstimulation for poor ovarian responders undergoing in vitro fertilisation/intracytoplasmic sperm injection: a protocol for systematic review and Bayesian network meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-039122 ◽

2021 ◽

Vol 11 (2) ◽

pp. e039122

Author(s):

Huisheng Yang ◽

Chensi Zheng ◽

Qiyan Zheng ◽

Huanfang Xu ◽

Xiaotong Li ◽

...

Keyword(s):

Pregnancy Rate ◽

Intracytoplasmic Sperm Injection ◽

Ovarian Stimulation ◽

Meta Analysis ◽

Ovarian Response ◽

Controlled Ovarian Hyperstimulation ◽

In Vitro Fertilisation ◽

Ovarian Hyperstimulation ◽

Poor Ovarian Responders

IntroductionControlled ovarian hyperstimulation (COH) is the routine regimen used to generate a sufficient number of follicles during in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Poor ovarian response is a challenge encountered by many clinicians during COH and poor ovarian responders (PORs) usually have higher follicle stimulating hormone levels, lower levels of anti-Mullerian hormone and few oocytes retrieved, which have been attributed mainly to advanced maternal age and poor follicle reserve or other reasons that could impair ovarian response during ovarian stimulation. Over the last few decades, researchers have proposed a series of strategies and ovarian stimulation protocols to improve pregnancy outcomes in patients with POR during their IVF/ICSI treatment. However, clinical decisions regarding COH protocols in PORs during IVF/ICSI treatment remain controversial. Traditional pairwise meta-analysis only allows the direct comparison of two protocols in COH for patients with POR. However, many of these COH protocols have not been compared directly in randomised controlled trials (RCTs). Thus, we aim to use network meta-analysis (NMA) to assess the clinical effectiveness and safety of COH protocols and to generate treatment rankings of these COH protocols for the most clinically important and commonly reported outcomes events.Methods and analysisThe PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, WanFang database and Chongqing VIP information databases will be searched for all RCTs of COH for POR women during IVF/ICSI from inception to 31 March 2020. Primary outcomes will include live birth rate and number of oocytes retrieved. Secondary outcomes will include ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, ovarian hyperstimulation syndrome rate, multiple pregnancy rate and cycle cancellation rate. Pairwise meta-analysis and Bayesian NMA will be conducted for each outcome. Subgroup analysis, meta-regression, and sensitivity analysis will be performed to assess the robustness of the findings. The generation of NMA plots and subsequent results will be performed by using R V.4.0.1. The assessment of confidence in network estimates will use the Confidence in Network Meta-Analysis)web application (see https://cinema.ispm.unibe.ch/).Ethics and disseminationThis review does not require ethics approval and the results of the NMA will be submitted to a peer-review journal.

Download Full-text