Clinical trial NCT05759871: Ovarian Stimulation With FSH Alone Versus FSH Plus GnRH Antagonist in an Oocyte Donor/Recipient Programme
Official title: Ovarian Stimulation With FSH Alone Versus FSH Plus a GnRH Antagonist in an Oocyte Donor/Recipient Programme: a Protocol for a Non-randomised Multicenter Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Premature Luteinisation
Progesterone Elevation
Keywords: Controlled ovarian stimulation
GnRH antagonist
oocyte donation
LH surge
Lead sponsor: National and Kapodistrian University of Athens
Sponsor class: OTHER
Collaborators: name: Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
name: Embryoland, Athens, Greece
name: Embryolab IVF Unit, Thessaloniki, Greece
name: Assisting Nature IVF Unit, Thessaloniki, Greece
name: HYGEIA IVF - Embryogenesis A.R.T. Unit, Athens, Greece
name: Institute of Fertility, Athens, Greece
name: Mitosis IVF Centre, Pireas, Greece
First posted: 2023-03-08
Enrollment: 50
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 32
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Protocol using FSH alone with that of a protocol using FSH plus a GnRH antagonist for controlled ovarian hyperstimulation in cycles of elective freezing in the context of a donor/recipient programme.
Primary purpose: TREATMENT

Brief summary: The aim of this study is to compare the efficacy of a protocol using FSH alone with that of a protocol using FSH plus a GnRH antagonist for controlled ovarian hyperstimulation in cycles of elective freezing in the context of a donor/recipient programme.

Detailed description: The hypothesis to be tested is that an ovarian stimulation protocol that includes FSH alone without any LH surge prevention regimens is not inferior to a protocol including FSH plus a GnRH antagonist in terms of clinical outcome in a donor/recipient model.

The formal sample size is calculated as follows:

If there is a true difference in favour of the experimental treatment of 5% (20% vs 15%), then 160 patients (80 per group in case of 1:1 enrolment) are required to be 80% sure that the upper limit of a one-sided 95% confidence interval (or equivalently a 90% two-sided confidence interval) will exclude a difference in favour of the standard/control group of more than 10%.

In the context of the present pilot study (as a first stage), the investigators intend to study 50 patients (25 per group in case of 1:1 enrolment). At a second stage the above mentioned sample size will be used.

Eligibility criteria: Inclusion Criteria:

* healthy women 21-32 years old with a BMI of 21 to 29 kg/m2 who wish to donate their oocytes
* normal ovarian reserve tests
* normal menstrual cycles of 26-32 days
* the women would not have received any hormonal treatment during the last three months before entering the study.

  * absence of coagulation and/or autoimmune disorders.

Exclusion Criteria:

1. Use of other protocols towards oocyte retrieval, such as natural, or modified natural cycles
2. Poor ovarian response according to the Bologna criteria \[22\],
3. History of endocrine or metabolic disorders, ovarian cystectomy or oophorectomy,
4. Women with the diagnosis of polycystic ovary syndrome
5. Clinical and/or laboratory markers of hereditary or acquired thrombophilia that complied to the standard protocols of each Unit.

   * Non-hormonal medication for a serious medical condition

Primary outcomes:
measure: Rate of LH secretory peaks
timeFrame: 3 weeks after start of ovarian stimulation.
measure: Rate of concentration of progesterone >1 ng/ml
timeFrame: At any time within 3 weeks after start of ovarian stimulation.
Secondary outcomes:
measure: Rate of ongoing clinical pregnancy
timeFrame: 12 weeks after last menstrual period
measure: Rate of miscarriage
timeFrame: Within 20 weeks after last menstrual period
Other outcomes:
measure: Total dose of gonadotrophins (rFSH)
timeFrame: 2 weeks after last menstrual period
measure: Number of retrieved cumulus oocytes complexes (COCs)
timeFrame: 3 weeks after last menstrual period / and start of ovarian stimulation
Locations:
Study officials:
References:
citation: Wang HL, Lai HH, Chuang TH, Shih YW, Huang SC, Lee MJ, Chen SU. A Patient Friendly Corifollitropin Alfa Protocol without Routine Pituitary Suppression in Normal Responders. PLoS One. 2016 Apr 21;11(4):e0154123. doi: 10.1371/journal.pone.0154123. eCollection 2016.
citation: Zhang Y, Xu Y, Yu J, Wang X, Xue Q, Shang J, Yang X, Shan X. A premature luteinizing hormone surge without elevated progesterone levels has no adverse effect on cumulative live birth rate in patient undergoing a flexible GnRH antagonist protocol: a retrospective study. J Ovarian Res. 2023 Jun 27;16(1):119. doi: 10.1186/s13048-023-01219-w.
citation: Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, Ai A, Shoham Z. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 2015 Jul;104(1):62-70.e3. doi: 10.1016/j.fertnstert.2015.03.022. Epub 2015 May 5.
citation: Messinis IE, Messini CI, Anifandis G, Daponte A. Exogenous progesterone for LH surge prevention is redundant in ovarian stimulation protocols. Reprod Biomed Online. 2021 Apr;42(4):694-697. doi: 10.1016/j.rbmo.2021.01.017. Epub 2021 Jan 30.
citation: Messinis IE, Templeton A, Baird DT. Endogenous luteinizing hormone surge in women during induction of multiple follicular development with pulsatile follicle stimulating hormone. Clin Endocrinol (Oxf). 1986 Feb;24(2):193-201. doi: 10.1111/j.1365-2265.1986.tb00762.x.