Ovarian Stimulation With FSH Alone Versus FSH Plus GnRH Antagonist in an Oocyte Donor/Recipient Programme
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: FSH only (no GnRH antagonist) Women receive only FSH starting on day 2 of the cycle. The starting dose of FSH is 225-300 IU s.c. for the first 4 days adjusted thereafter according to the ovarian response. |
Other: GnRH antagonist
The GnRH antagonist in the control group (standard therapy) is administered from day 6 of FSH treatment at the dose of 0.25 mg per day until the triggering day and is injected each time immediately after the injection of FSH.
|
| Active Comparator: FSH + GnRH antagonist Women receive 225-300 IU s.c. FSH, and a GnRH antagonist from day 6 of FSH treatment at the dose of 0.25 mg per day until the triggering day. The GnRH antagonist in group 2 is injected each time immediately after the injection of FSH. |
Other: GnRH antagonist
The GnRH antagonist in the control group (standard therapy) is administered from day 6 of FSH treatment at the dose of 0.25 mg per day until the triggering day and is injected each time immediately after the injection of FSH.
|
Outcome Measures
Primary Outcome Measures
- Rate of LH secretory peaks [3 weeks after start of ovarian stimulation.]
A secretory peak of LH is defined as the increase at levels ≥10 IU/l.
- Rate of concentration of progesterone >1 ng/ml [At any time within 3 weeks after start of ovarian stimulation.]
Concentration of progesterone elevation >1 ng/ml
Secondary Outcome Measures
- Rate of ongoing clinical pregnancy [12 weeks after last menstrual period]
Clinical pregnancy (fetal heart beat) at ultrasound
- Rate of miscarriage [Within 20 weeks after last menstrual period]
Miscarriage / Loss of the embryo
Other Outcome Measures
- Total dose of gonadotrophins (rFSH) [2 weeks after last menstrual period]
Dose of rFSH administered
- Number of retrieved cumulus oocytes complexes (COCs) [3 weeks after last menstrual period / and start of ovarian stimulation]
Number of retrieved cumulus oocytes complexes (COCs) at oocyte retrieval
Eligibility Criteria
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:
-
Use of other protocols towards oocyte retrieval, such as natural, or modified natural cycles
-
Poor ovarian response according to the Bologna criteria [22],
-
History of endocrine or metabolic disorders, ovarian cystectomy or oophorectomy,
-
Women with the diagnosis of polycystic ovary syndrome
-
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- National and Kapodistrian University of Athens
- Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
- Embryoland, Athens, Greece
- Embryolab IVF Unit, Thessaloniki, Greece
- Assisting Nature IVF Unit, Thessaloniki, Greece
- HYGEIA IVF - Embryogenesis A.R.T. Unit, Athens, Greece
- Institute of Fertility, Athens, Greece
- Mitosis IVF Centre, Pireas, Greece
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- Yangyang Zhang et al. Effect of a premature luteinizing hormone surge on cumulative live birth rate during a flexible GnRH antagonist protocol: a retrospective study. https://doi.org/10.21203/rs.3.rs-1361146/v1
- Non-anta-D