Optimal Planning of a Day 3 Cryopreserved(Frozen)-Thawed Embryo Transfer in a Natural Cycle With hCG Administration or After Spontaneous LH Peak? (PLUS)

Universitair Ziekenhuis Brussel

Status and phase: Completed; Phase 4

Conditions: Supervision of Pregnancy Resulting From In-vitro Fertilization

Treatments: Drug: hCG; Other: LH peak

Study type: Interventional

Funder types: Other

Identifiers

NCT02145819

PLUS

Details and patient eligibility

About

The aim of the study is to determine whether spontaneous LH peak is superior to human chorionic gonadotropin before a transfer of a day 3 frozen embryo.

Full description

For surplus embryos after fresh IVF-cycles, cryopreservation has become common medical practice. These frozen embryos are mostly replaced in an artificial cycle with exogenous estrogen and progesterone or in a natural cycle. Often, hCG is administered as an ovulation induction agent for scheduling purposes.

Successful implantation requires a co-ordinated series of events allowing a timely dialogue between a receptive endometrium and the intrusive blastocyst . The period of receptivity is thought to be 3 days in human. It is suggested that blastocyst apposition begins about day LH+6 and is completed by day LH+10

In general, the aim is to transfer the embryo during the 'window of implantation', what is defined as the period during which the uterus is receptive for implantation of the free-lying blastocyst. This has been a subject of debate since many years.

A prospective study by Fatemi et al. (2010) revealed a significantly higher ongoing pregnancy rate after transferring frozen-thawed embryos in natural cycles with a spontaneous LH peak compared with natural cycles controlled by hCG for final oocyte maturation and ovulation (31.1% vs. 14.3%, respectively). In this trial, FrET (frozen embryo transfer) was planned 5 days after the LH surge or 5 days after the administration of 5000IU of hCG.

In order to optimize the synchronization in the hCG group, and therefore enhance the pregnancy rates, the aim is to plan a FrET 6 days after hCG administration instead of 5 days. The rationale behind is that day 3 frozen embryos are thawed the day before embryo transfer, which means they are already at day 4 of the embryonic development.

Enrollment: 240 patients

Sex: Female

Ages: 18 to 39 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Natural cycles, in which a frozen-thawed day 3 embryo is replaced.
• Signed informed consent.
• Regular cycle (i.e. between 26 and 35 days)
• Normal transvaginal ultrasound at screening, without evidence of clinically significant abnormality consistent with finding adequate for ART with respect to uterus and adnexa.
• Embryos frozen by vitrification.
• Single or dual embryo transfer.

Exclusion criteria

• Known allergic reactions to progesterone products.
• Intake of experimental drug within 30 days prior to study start.
• Contraindication for pregnancy.
• Embryos of women above 39 years of age at the time of embryo freezing.
• Recipients of oocyte donation cycles

Trial design

240 participants in 2 patient groups, including a placebo group

A: spontaneous LH peak

Placebo Comparator group

Description:

In group A, embryos are thawed 4 days after LH surge, with a re-evaluation and transfer 5 days after LH surge.

Treatment:

Other: LH peak

B: hCG

Active Comparator group

Description:

In group B, embryos are thawed 5 days after hCG administration, with a re-evaluation and transfer 6 days after hCG.

Treatment:

Drug: hCG