Clinical trial NCT03701490: Prolutex in Frozen Embryo Transfer Cycles At the Blastocyst Stage (PROGEX)
Official title: A Proof of Concept, Randomized, Controlled Clinical Trial to Assess the Efficacy of Subcutaneous Progesterone (Prolutex) Versus Vaginal Progesterone (Progeffik) for Endometrial Preparation in Women Undergoing Frozen Embryo Transfer(FET) Cycles
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infertility
Lead sponsor: IBSA Institut Biochimique SA
Sponsor class: INDUSTRY
First posted: 2018-10-10
Enrollment: 213
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this proof of concept clinical trial is to evaluate the impact of two different progesterone treatments for endometrial preparation (25 mg/twice-a-day, subcutaneous injection, and 200 mg/three times a day, vaginal administration) on the clinical pregnancy rate in women undergoing frozen embryo transfer (FET) at blastocyst stage.


Eligibility criteria: Inclusion Criteria:

* Women attending the clinics to undergo a frozen blastocyst embryo transfer, having given written informed consent, with the following characteristics:
* 18-49 years of age for subjects undergoing ET with donated oocytes (both inclusive);
* 18-37 years of age for subjects undergoing ET with autologous oocytes (both inclusive);
* BMI \<32 kg/m2;
* Adequate endometrium preparation (Endometrial thickness \> 7 mm) and E2 levels ( \>100 pg/ml) on the day progesterone treatment is started;
* P4 levels \<1.5 ng/ml on the day progesterone treatment is started;
* Transfer of 1 or 2 frozen embryos at blastocyst stage
* Transfer of frozen embryos of quality A and/or B according to Gardner criteria1;
* Semen from ejaculation either from the partner or from a bank
* ≤ 3 previous ET (frozen and fresh) with no pregnancy
* Normal uterine cavity (i.e. no polyp or protruding sub-mucosal fibroid).

Exclusion Criteria:

* Presence of functional follicles \> 10 mm of diameter on the day progesterone treatment is started;
* Intramural uterine fibroids that distort the uterine cavity or polyps \>1 cm;
* Stage III or IV endometriosis (endometriomas);
* Hydrosalpinx;
* Pregnancy or lactation
* Malformations of the sexual organs incompatible with pregnancy;
* Patients affected by pathologies associated with any contraindication of being pregnant;
* Known allergy to progesterone preparations or their excipients;
* Uncontrolled adrenal or thyroid dysfunction;
* Undiagnosed vaginal haemorrhage;
* History of, or current arterial disease;
* Patients with hepatic impairment;
* HIV, Hepatitis B Virus or Hepatitis C Virus seropositive;
* Neoplasias (current) or history of neoplasia that may be responsive to progesterone;
* High grade cervical dysplasia;
* Active thrombophlebitis or thromboembolic disorders, or a history of hormone-associated thrombophlebitis or thromboembolic disorders;
* Currently dependent on alcohol, drugs or psychotropic drugs
* History of recurrent pregnancy loss defined as 3 or more spontaneous miscarriages wherein pregnancy developed to a minimum of a gestational sac on transvaginal ultrasonography;
* Participation in a concurrent clinical trial or another trial within the past 2 months;
* Use of concomitant medications that might interfere with the study evaluation: hormonal treatments other than those used in the study, except thyroid hormones.

Primary outcomes:
measure: Clinical pregnancy rate
timeFrame: 4-5 weeks after progesterone treatment start.
Secondary outcomes:
measure: Serum progesterone level
timeFrame: 19+/-2 days and 4-5 weeks after start progesterone treatment
measure: Frequency of uterine contractions
timeFrame: on the day of Embryo transfer (i.e. 5 days after start progesterone treatment)
measure: Positive serum pregnancy (beta-hCG) test rate
timeFrame: 19+/-2 days after start progesterone treatment
measure: Implantation rate
timeFrame: 4-5 weeks after start progesterone treatment.
measure: Ongoing pregnancy rate
timeFrame: 9-11 weeks after start progesterone treatment.
measure: Abortion rate
timeFrame: 9 months after start progesterone treatment.
Other outcomes:
Locations:
city: Alicante
country: Spain
facility: Instituto Bernabeu
city: Madrid
country: Spain
facility: Instituto Bernabeu Madrid
city: Sevilla
country: Spain
facility: Ginemed
Study officials:
References: