Clinical trial NCT02825290: Modified Luteal Support for Frozen-Thawed Embryo Transfer - A Prospective Study
Official title: Modified Luteal Support for Frozen-Thawed Embryo Transfer - A Prospective Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Embryo Transfer
Luteal Support
Keywords: Frozen-thawed embryo transfer (FET)
Luteal support
Progesterone
Natural cycle
Cryopreservation
IVF
hCG
GnRH-Agonist
Pregnancy rate
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2016-07-07
Enrollment: 62
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates the outcomes of frozen-thawed embryo transfer (FET) success rate with modified luteal support - addition of a single injection of HCG and GnRH-agonist, on day of ET and 4 days later, respectively vs. traditional luteal support with vaginal progesterone only in ovulating women.

Detailed description: Background With the recent trend toward single embryo transfer (ET) adopted in an attempt to reduce the risk of multiple pregnancy, the remaining extra embryos are cryopreserved, providing further possibilities for conception after the initial fresh transfer. Moreover, several studies that compared fresh and frozen-thawed embryo transfer (FET) cycles in normal responders have demonstrated a significantly higher clinical pregnancy rate per transfer in the FET versus the fresh cycles.

There are several currently employed replacement protocols for FET. The choice of protocol depends on the individual woman's ovarian function and convenience of the method, as well as on the experience gained with the method by the physicians. Whatever protocol is used, the success requires optimal synchronization between the embryonic stage at thawing and date of the endometrium within the endometrial preparation cycle. While there is a consensus regarding the duration, route of delivery and dosage of estrogen supplementation, and the optimal ultrasonographic endometrial appearance and thickness, the effect of the different modes of luteal support remains unclear.

Prompted by the study demonstrating higher ongoing pregnancy rate following the transfer of frozen-thawed embryos in natural cycles with spontaneous LH rise compared with natural cycles controlled by hCG for final oocyte maturation and the reports showing improved pregnancy rate in patients who received a mid-luteal injection of a GnRH-agonist (0.1 mg triptorelin), the investigators started beginning at June 2014 to offer ovulatory patients with regular menstrual cycles a natural FET with modified luteal support. Starting on the day of spontaneous ovulation, patients received daily vaginal progesterone, supplemented by a single injection of HCG and GnRH-agonist, on day of ET and 4 days later, respectively.

The results for this study were very promising - the investigators were able to show a significant increase in implantation rate (30% vs. 17%; p\<0.03), clinical pregnancy (48% vs. 26%; p\<0.01) and ongoing pregnancy (39% vs. 20%; p\<0.01) for the patients receiving the aforementioned modified luteal support protocol.

After the completion of this retrospective study the investigators are heading to prove the superiority of the modified luteal support protocol for ovulatory patients by conducting a prospective study.

Materials \& Methods Study design - A prospective, randomized, blinded study. Primary endpoint - Ongoing pregnancy. Secondary endpoints - Implantation rate, clinical pregnancy. Study sample - According to the previous, retrospective study the investigators will need 31 patients in each study arm in order to show an increase from 20% clinical pregnancy to 39% (confidence level 5%, beta error level 50%).

The patients - The investigators will offer each patient treated in the unit for frozen-thawed embryo transfer to participate in the study. The randomization of the participants will be on the day of embryo transfer with a computer program on a 1:1 enrollment ratio.

All transfers will be performed by an experienced physician who will be blinded to the luteal support protocol.

Both groups will be treated with the accepted progesterone luteal support - starting on ovulation day - vaginal progesterone 90 mg (Crinone; Merck Serono, Hellerup, Denmark) once a day.

Study group - Patients in the study group will receive additional two injections - the first - recombinant hCG 250 mcg (Ovitrelle; Merck Serono) on the transfer day and the second - GnRH-agonist 0.1 mg (Decapeptyl; Ferring Pharmaceuticals Israel) 4 days after the embryo transfer day. Patients in the control group will receive no injection.

B-hCG levels will be examined 12 days after embryo transfer and if positive ultrasound examinations will be performed as usual to document pregnancy outcome.

The data - The investigators will use demographic data such as age, BMI, gynecological data as gravida, para, etiology of infertility and data about previous \& current IVF treatments such as number of treatments, stimulation protocol, hormone levels, number of oocytes, embryos' characteristics, etc.

Statistics - Statistical analysis will be performed with Student's t-test and Chi square, as appropriate. Results will be presented as means ± standard deviations; p\<0.05 will be considered significant.

Eligibility criteria: Inclusion Criteria:

* 20-40 years old women
* Spontaneously ovulating women
* Treated in our IVF unit for frozen-thawed embryo transfer
* At least one top quality embryo

Exclusion Criteria:

* PGD patients
* More than 4 previous embryo transfers

Primary outcomes:
measure: Ongoing pregnancy
timeFrame: About 10-12 weeks after embryo transfer
Secondary outcomes:
measure: Implantation rate
timeFrame: 2 weeks after embryo transfer
measure: Clinical pregnancy
timeFrame: About 3-4 weeks after embryo transfer
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Sheba medical center
Study officials:
References:
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