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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed 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.

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

Conditions
-----------------
Supervision of Pregnancy Resulting From In-vitro Fertilization

Intervention / Treatment
-----------------
* Drug: hCG
* Other: LH peak


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: A: spontaneous LH peak<br>In group A, embryos are thawed 4 days after LH surge, with a re-evaluation and transfer 5 days after LH surge. | Other: LH peak<br> <br> |
| Active Comparator: B: hCG<br>In group B, embryos are thawed 5 days after hCG administration, with a re-evaluation and transfer 6 days after hCG. | Drug: hCG<br> <br> * Other names: spontaneous LH peak;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical pregnancy rate | We evaluate the pregnancy, at 7 weeks amenorrhoea. Outcome is clinical pregnancy rate | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of monitoring visits at the clinic per cycle |  | 7 weeks |