Ovarian Stimulation

Women with a severely diminished ovarian reserve and monofollicular growth are at a higher risk of premature ovulation as well as poor quality oocytes. Our group showed previously that women with severely diminished ovarian reserve benefit from receiving the final oocyte maturation at smaller follicle sizes in terms of reducing the risk of premature ovulation and finding mature oocytes even out of small size follicles. Adding the measurement of the follicular volume at the time of final oocyte maturation might provide more information on the proper timing of trigger administration compared to the follicular size alone, hormonal profile as well as previous stimulation attempts. Setting a cutoff value of follicular volume for trigger might help to avoid premature ovulation and possibly increase the chances of ending up with a euploid embryo.

This study examines if monitoring serum Follicle Stimulation Hormone (FSH) levels can predict oocyte yield and progesterone levels, considering factors like age, baseline FSH, Antral Mullerian Hormone (AMH), antral follicle count, body weight, kidney function, and urinary FSH. The aim is to find a minimum FSH level that ensures optimal ovarian response and enables tailored FSH dosages for better outcomes.

To evaluate, in a randomized controlled trial, whether AI-guided monitoring and ovulation triggering leads to clinical outcomes comparable to those achieved through physician-led decision-making in patients undergoing ovarian stimulation for IVF.

P-CCROSS is a randomized, prospective monocentric phase 4 study with a crossover study design. The aim of the study is to compare patient satisfaction (by means of questionnaires) and treatment compliance with IVF treatment with CFA (corifollitropin alfa) and PPOS (Progestin-Primed Ovarian Stimulation) versus conventional IVF treatment with a recombinant FSH/GnRH antagonist. The study will also compare patients undergoing elective fertility preservation versus PGT-A (pre-implantation genetic testing for aneuploidy) patients.The study will have a crossover design so that patients will receive both forms of treatment. The investigators will also compare the endocrine profile and ovarian response of CFA/PPOS versus rFSH/GnRH ovarian stimulation cycles.

Stimulation is a key step of in vitro fertilization (IVF). Typically, injectable gonadotropins are used for stimulation, and their dose is individually determined to avoid hypo- as well as hyper-response. Despite the individualization some patients respond with a lower-than-expected number of oocytes. If the low response is unexpected based on the baseline parameters or if an unusually high dose of gonadotropins is needed to achieve a proper response we talk about "hypo-response". In such cases if the first treatment fails and a repeat attempt is planned typically even more gonadotropins, the combination of luteinizing hormone (LH) with follicle stimulating hormone (FSH) or the use of the more potent recombinant preparations are considered. The benefits of these approaches however have not been studied properly in hypo-responders. The studies have used various criteria to identify hypo-responders, have used various gonadotropin doses and have evaluated different outcome parameters. Live birth was only studied in one trial. It is also known that in a different cycle the same patient is likely to have a slightly different response to the same type and dose of drugs. Therefore, the question arises whether a hypo-responder in one treatment is expected to have hypo-response again if the treatment is similarly carried out in a different cycle. Do we need to change/ increase the gonadotropin dose if based on age and ovarian reserve otherwise we would expect a normal response? Furthermore, if we consider a change should we increase the dose of FSH or should we combine it with LH? Therefore the aim of this randomized controlled trial is compare an unchanged medication regimen to increased dose of FSH vs the combination of FSH and LH in hypo-responder patients identified based on POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) criteria (Gr 1 and 2: retrieval of 9 or fewer oocytes in patients with an anti-Müllerian hormone (AMH) level ≥ 1.2 ng/ml or antral follicle count (AFC) ≥ 5 and age \<35 years \[Group (Gr) 1\] or ≥35 years \[Gr2\]). Hypo-responder patients will be randomized to: 1. Same gonadotropin dose as in previous treatment (recombinant(r) FSH) \['control group'\] 2. The same dose as in the previous cycle but in the form of FSH + LH combination (rFSH:rLH 2:1 ratio) \['additional LH group'\] 3. A dose increase of 75 international unit (IU) compared to the dose in the previous treatment. \['higher dose FSH group'\] The primary outcome parameter to study is live clinical pregnancy. In addition, baseline demographic, stimulation and further clinical outcomes (pregnancy rate, miscarriage rate, live birth rate) will be compared.

Gonal-F® (follitropin alfa) is a recombinant FSH without LH activity, while Menopur® contains both LH and hCG. The MEGASET trial compared Menopur® and Gonal-F® in GnRH antagonist cycles with SET, showing similar efficacy. A subsequent study (MEGASET-HR) in high responders found ongoing pregnancy rates of 35.5% for Menopur® and 30.7% for Gonal-F®, with a lower early pregnancy loss for Menopur® (14.5% vs 25.5%). Telomere length (TL) in oocyte cumulus cells (CC) correlates with oocyte quality and embryo outcomes. This study aims to assess whether stimulation type (hMG vs. Gonal-F) affects TL in CC and subsequent blastocyst development. A randomized, open-label, cross-over study in normo-responders will analyze telomere length, embryo quality, and hormonal markers.