Dose adjustment of follicle-stimulating hormone (FSH) during ovarian stimulation as part of medically-assisted reproduction in clinical studies: a systematic review covering 10 years (2007–2017)

Abstract

Background Individualization of the follicle-stimulating hormone (FSH) starting dose is considered standard clinical practice during controlled ovarian stimulation (COS) in patients undergoing assisted reproductive technology (ART) treatment. Furthermore, the gonadotropin dose is regularly adjusted during COS to avoid hyper- or hypo-ovarian response, but limited data are currently available to characterize such adjustments. This review describes the frequency and direction (increase/decrease) of recombinant-human FSH (r-hFSH) dose adjustment reported in clinical trials. Methods We evaluated the proportion of patients undergoing ART treatment who received ≥ 1 r-hFSH dose adjustments. The inclusion criteria included studies (published Sept 2007 to Sept 2017) in women receiving ART treatment that allowed dose adjustment within the study protocol and that reported ≥ 1 dose adjustments of r-hFSH; studies not allowing/reporting dose adjustment were excluded. Data on study design, dose adjustment and patient characteristics were extracted. Point-incidence estimates were calculated per study and overall based on pooled number of cycles with dose adjustment across studies. The Clopper–Pearson method was used to calculate 95% confidence intervals (CI) for incidence where adjustment occurred in < 10% of patients; otherwise, a normal approximation method was used. Results Initially, 1409 publications were identified, of which 318 were excluded during initial screening and 1073 were excluded after full text review for not meeting the inclusion criteria. Eighteen studies (6630 cycles) reported dose adjustment: 5/18 studies (1359 cycles) reported data for an unspecified dose adjustment (direction not defined), in 10/18 studies (3952 cycles) dose increases were reported, and in 11/18 studies (5123 cycles) dose decreases were reported. The studies were performed in women with poor, normal and high response, with one study reporting in oocyte donors and one in obese women. The median day that dose adjustment was permitted was Day 6 after the start of treatment. The point estimates for incidence (95% CI) for unspecified dose adjustment, dose increases, and dose decreases were 45.3% (42.7, 48.0), 19.2% (18.0, 20.5), and 9.5% (8.7, 10.3), respectively. Conclusions This systematic review highlights that, in studies in which dose adjustment was allowed and reported, the estimated incidence of r-hFSH dose adjustments during ovarian stimulation was up to 45%.

The Essential Role of Body Weight in Adjusting Gn Dosage to Prevent High Ovarian Response for Women With PCOS During IVF: A Retrospective Study

“…For young women with AFC>15, rFSH dose (IU per kg) was related to ovarian response, and the starting dose of rFSH adjusted for body weight had a prediction role on day 5 median follicle size and the proportion of antral follicles recruited, when adjusted by age, AFC, and pre-treatment FSH level (9). Several factors have been put forward to adjust the Gn dose during COS, including ovarian response, AMH, and AFC (6,15,16). Involving two or more factors could help improve COS results significantly.…”

“…Individualized exogenous gonadotropin (Gn) dose is essential for minimizing OHSS risk and optimizing follicle recruitment at the same time. The strategies to manage OHSS include initial dosage selection and dose adjustment during cycle (6). Several studies have developed a series of algorithms to predict the proper initial dosage of Gn based on age, Anti-Mullerian hormone (AMH), body mass index (BMI), baseline follicle stimulating hormone (FSH) level, or ovarian response of the previous cycle (7).…”

Real-world observational study to capture practice pattern of controlled ovarian stimulation in the in vitro-fertilization and embryo transfer or intracytoplasmic sperm injection-2

“…A dose of 100-225 IU is considered the standard gonadotropin daily dose. 34 GnRH agonists have been used to trigger final oocyte maturation in GnRH antagonist cycles. 35 As per existing literature, a lower probability of pregnancy is expected when a single dose of GnRH agonist is used instead of hCG for triggering final oocyte maturation.…”

Self-Monitoring of Urinary Hormones in Combination with Telemedicine — a Timely Review and Opinion Piece in Medically Assisted Reproduction

“…gonadotropin-releasing hormone [GnRH] agonist or antagonist), gonadotropin type and dose, type of trigger of final oocyte maturation and type and duration of luteal phase support, are essential to ensure that the patient’s response to treatment is optimized with respect to efficacy and safety [ 2 , 23 – 25 ]. To this end, starting dose selection according to predicted ovarian response prior to stimulation, and dose adjustments during treatment cycle are frequently performed in fertility clinics [ 26 , 27 ]. Assessment of hormonal profile plays an important role in almost all aspects of individualized fertility treatment, but particularly in guiding intra-cycle dose adjustments, as these are directly based on ultrasound assessment of follicular development and monitoring of serum hormones [ 20 ].…”