Comparison of Vaginal and Transdermal Oestrogen Before Frozen Thawed Embryo Transfer

Study Overview
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Brief Summary
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The purpose of this study is to compare pregnancy outcomes of frozen-thawed embryo transfer after endometrial preparation with vaginal estradiol or transdermal estradiol and to evaluate women's satisfaction

Detailed Description
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Frozen-thawed transfer embryo are more and more frequent but to date, there is no consensus on the ideal management of the adequate endometrial preparation. Artificial preparation of endometrium is commonly used in assisted reproduction center because it is more easy to schedule. Estradiol could be administrate by oral, vaginal or transdermal, but no protocol seems to improve clinical pregnancy rates. To investigator's knowledge, transdermal estradiol has never been compare to vaginal administration before frozen-thawed embryo transfer. Because transdermal administration could improve satisfaction of patients and reduce duration of treatment (when compare to oral administration), the investigators conduct a prospective study to compare clinical pregnancy rate after transdermal or vaginal estradiol administration to prepare the endometrium before frozen-thawed embryo transfer. The investigator also evaluate side effects and patients satisfaction in both protocol. The patients choose if they prefer vaginal or transdermal protocol after receiving sufficient information during medical consultation.

Official Title
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Endometrial Estrogen Preparation Before Frozen-thawed Embryo Transfer : Comparison of Vaginal and Transdermal Administration

Conditions
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Embryo Transfer, Infertility

Intervention / Treatment
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* Drug: Estradiol 2 MG
* Drug: Estradiol 100 µg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 18 and <43 frozen-thawed embryo transfer after exogenously administered estrogen in either way transdermal or vaginal patients who accepted being included and signed the consent forms. Exclusion Criteria: patient who refuse to participate frozen-thawed embryotransfer after stimulated or natural cycle oocyte or sperm donation endometrial thickness after 21 days <6mm non-french speaking patients women under legal guardianship women with no health or social security coverage

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 43 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| transdermal<br>transdermal estradiol (Vivelledot, Novartis) 100 µg on day 3, then 200 µg day 7 and every 4 days, until first pregnancy test. If pregnancy test is positive, treatment is to continue until 8 weeks. | Drug: Estradiol 100 µg<br>* transdermal estradiol (Vivelledot, Novartis) 100 µg on day 3, then 200 µg day 7 and every 4 days, until first pregnancy test. If pregnancy test is positive, treatment is to continue until 8 weeks.<br>* Other names: vivelledot 100 µg;|
| vaginal<br>Vaginal estradiol (Provames, Sanofi) 4mg per day from day 3 to first pregnancy test. If pregnancy test is positive, treatment is to continue until 8 weeks | Drug: Estradiol 2 MG<br>* Vaginal estradiol (Provames, Sanofi) 4mg per day from day 3 to first pregnancy test. If pregnancy test is positive, treatment is to continue until 8 weeks<br>* Other names: provames 2mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical pregnancy | defined as fetal cardiac activity at 12 weeks of gestation | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| chemical pregnancy | Defined as serum HCG levels >10 IU/L, 14 days after the embryo transfer, followed by a rapid decrease until being undetectable | 6 weeks | 
| spontaneous pregnancy loss | Including early and late pregnancy losses | 12 weeks | 
| plasmatic estradiol concentration on the day of transfer | plasmatic estradiol concentration on the day of transfer | 21 days | 
| plasmatic lh concentration on the day of transfer | plasmatic lh concentration on the day of transfer | 21 days | 
| plasmatic progesterone concentration on the day of transfer | plasmatic progesterone concentration on the day of transfer | 21 days | 
| endometrial thickness | sonographic measurement of endometrial thickness on the day of transfer | 21 days | 
| annulation | defined when transfer is cancel if endometrial thickness is too thick (>6-7mm), when spontaneous ovulation is found with progesterone plasmatic increase and corpus luteum is seen by sonography or when unpredictable events occur (infections, ZIKA suspicion, endometriosis crisis, bad observance…). Annulation could be decided by biologist in case of embryo's lysis or bad quality seen after thawing. | 21 days | 
| treatment duration | duration of treatment before transfer | 21 days | 
| satisfaction evaluated by anonymous survey the day of transfer | evaluated by anonymous survey the day of transfer | 1 month |