Luteal Phase Support With GnRH Agonist After GnRH Agonist Triggering in IVF/ICSI Cycles (SOLOAGO)

Assistance Publique - Hôpitaux de Paris

Status and phase: Enrolling; Phase 3

Conditions: In Vitro Fertilization; ICSI Intracytoplasmic Spermatozoid Injection

Treatments: Drug: Ovulation induction with hCG + Luteal phase support with vaginal progesterone; Drug: Ovulation triggering by Triptorelin + Luteal phase support by Nafarelin

Study type: Interventional

Funder types: Other

Identifiers

NCT06150703

APHP220667

Details and patient eligibility

About

The development of stimulation protocols for in vitro fertilisation (IVF) has led to a paradox. It has now been established that obtaining a large number of oocytes is a key to success, but that it is also a risk factor for embryo transfer failure after puncture (disruption of endometrial receptivity due to luteal insufficiency) and a risk factor for complications such as ovarian hyperstimulation syndrome (OHSS).

Full description

It is currently established that obtaining a large number of oocytes is a key of success in IVF/ICSI cycles. However, it is also a risk factor for ovarian hyperstimulation syndrome (OHSS) and a risk factor of implantation failure after fresh embryo transfer because of the alteration of endometrial receptivity. A freeze all strategy can be proposed to avoid these risks but vitrification of embryos, although more efficient than slow freezing in terms of embryo survival, is not without risk. Furthermore, proper endometrial and embryo timing for frozen-thawed embryo transfer is still debated.

Recent preliminary works suggest another possible way to combine an optimal ovarian response with the recovery of a large number of oocytes, good chances of implantation and a reduced risk of OHSS. To achieve this goal, ovulation triggering and luteal phase support need to be modified together. The human chorionic gonadotropin (hCG) (mimicking the Luteinising Hormone (LH)peak to trigger ovulation) that induces OHSS is replaced by an a GnRH agonist (GnRHa) triggering allowing an endogenous peak of Follicle Stimulating Hormone (FSH) and LH. Then, the usual support of the luteal phase by exogenous vaginal progesterone, whose absorption seems to be suboptimal for about 30% of patients, is replaced by endogenous progesterone production by the corpora lutea, supported by the maintenance of LH activity through the continuation of agonist of gonadotropin releasing hormone (AgoGnRH) in the luteal phase. Pilot studies show that a 10% to 15% increase in ongoing pregnancy rates can be expected with this type of protocol. The objective of our study is to demonstrate an increase in ongoing pregnancy rate per cycle with this new strategy combining GnRHa triggering and GnRHa luteal phase support compared to the reference protocol (hCG triggering and exogenous progesterone luteal phase support).

Enrollment: 652 estimated patients

Sex: Female

Ages: 18 to 39 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients requiring conventional IVF or IVF with sperm injection (ICSI) from the partner or donor under the conditions of management defined by French law.
• Patients aged 18 to 39 included
• First or second attempt at IVF or ICSI for pregnancy
• BMI < 35 kg/m2
• Anti-Mullerian hormone (AMH) > 1 ng/ml (= 7 pmol/L) and/or antral follicle count ≥ 8 within the year prior to inclusion
• AMH < 5 ng/ml and/or antral follicle count <40 within the year prior to inclusion
• Treatment with recombinant FSH
• Antagonist protocol (with pre-treatment or not)
• Initial dose of recombinant FSH between 75 and 450 IU
• Signed informed consent
• Affiliation to the social security system (excluding AME)

Exclusion criteria

• Patient diagnosed with HIV infection
• ICSI with sperm from testicular biopsy
• Pre-implantation diagnosis
• Hypogonadotropic hypogonadism (amenorrhea or spaniomenorrhea with basal LH <1.2 IU/L)
• History of severe ovarian hyperstimulation syndrome (OHSS)
• Unoperated hydrosalpinx
• Intracavitary polyps or myomas deforming the cavity
• Known hypersensitivity to the investigational drugs and/or their excipients (human chorionic gonadotropin, progesterone, nafarelin acetate, GnRH, GnRH analogues, mannitol, sodium chloride, water for injection, glacial acetic acid, Sodium hydroxide and/or hydrochloric acid, sorbitol, purified water, benzalkonium chloride, sunflower oil, soybean lecithin, gelatin, glycerol, titanium dioxide (E171), methionine, poloxamer 18, phosphoric acid).
• Gynaecological bleeding or genital haemorrhage
• History of epilepsy and/or intracranial tumors potentially causing epilepsy
• Tumours of the hypothalamus or pituitary gland
• Ovarian enlargement or cysts unrelated to polycystic ovary syndrome
• Severe adenomyosis requiring a long protocol
• Carcinoma of the ovary, uterus or breast
• Active thromboembolic events
• Severe impairment of liver function
• Breastfeeding women
• Patients under court protection, guardianship or curators
• Current participation in another therapeutic interventional trial on the day of inclusion
• Patients who do not speak or understand French

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

652 participants in 2 patient groups

Ovulation triggering with hCG + Luteal phase support with vaginal progesterone

Active Comparator group

Description:

hCG 250µg subcutaneously between 36h and 38h before oocyte retrieval + Progesterone 600mg/d (200mg tid) vaginally from the evening of the oocyte retrieval until the first pregnancy test

Treatment:

Drug: Ovulation induction with hCG + Luteal phase support with vaginal progesterone

Ovulation triggering with Triptorelin + Luteal phase support with Nafarelin

Experimental group

Description:

Triptorelin 0.2 mg subcutaneously between 36h and 38h before oocyte retrieval as a single dose Nafarelin 400µg /day (200µg in the morning 200µg in the evening) nasally from the evening of the oocyte retrieval until the first pregnancy test

Treatment:

Drug: Ovulation triggering by Triptorelin + Luteal phase support by Nafarelin