Natural Cycle Versus Stimulated Cycle Before Frozen Embryo Transfer

Study Overview
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Brief Summary
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Embryo freezing is a technique used regularly to optimize the pregnancy rate in case of infertility. This method is performed in presence of supernumerary embryo(s) after fresh transfer, or after freeze all embryos in case of medical reasons. It is necessary to control that the transfer is performed when the endometrium is receptive, which is essential for embryo implantation and pregnancy. This period is defined as the implantation window. Endometrial preparation can be achieved by hormone replacement therapy (HRT) or moderate ovarian stimulation (SO). The implantation window can also be assessed by monitoring of a natural cycle (NC). The objectives of this open randomized study is to compare the number of visits (ultrasound and blood tests) induced by the SO or NC as well as the women quality of life in both groups.

Detailed Description
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For infertile couples supported by in vitro fertilization, embryo freezing is a technique used regularly to optimize the pregnancy rate per retrieval of oocytes. This method is performed in case of supernumerary embryo(s) after fresh embryo transfer, or freeze all of the embryonic cohort in case of medical reasons preventing the transfer. The embryo or embryos can then be thawed and transferred (FET) to achieve a live birth. However, it is necessary to first ensure that the transfer is carried out at a time when the endometrium is receptive, which is essential for embryo implantation and pregnancy. This period is defined as the implantation window. Endometrial preparation can be performed by hormone replacement therapy (HRT) or moderate ovarian stimulation (SO). The implantation window can also be assessed by the monitoring of a natural cycle (NC). The choice of the key moment for the transfer is determined by ovulation and / or the rise of progesterone. To date, no study has demonstrated the superiority of one protocol over another in terms of birth rates. In the investigative center, treatment is usually carried out by daily subcutaneous injections of gonadotrophins followed by ovulation induction. In this context, the implementation of the FET in natural cycle may appear less burdensome for the patient and more physiological. The consideration is additional constraints, NC imposing more frequent monitoring (ultrasound and / or hormone assays) to detect the ovulation peak and less freedom in choosing the date of transfer. The average number of visits with SO is 2.6 per cycle. The aim of this study is to compare the stresses and safety of these two therapeutic proposals to determine the least restrictive for patients.

Official Title
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Comparison of the Number of Visits and the Quality of Life Versus Natural Cycle in Stimulated Cycle Before Frozen Embryo Transfer

Conditions
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Fertility

Intervention / Treatment
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* Other: natural cycle
* Drug: moderate ovarian stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Affiliation to the general social security regime and benefiting from 100% infertility; Regular Cycles 26 to 35 days; Support in IVF or ICSI ; Existence of at least 2 frozen embryos to J2 or J3; Treated for their first or second cycle of TEC. Exclusion Criteria: Donor sperm; Irregular cycles and / or polycystic ovary syndrome; Embryos frozen at J1 or J5 / J6 or double planned transfer or transfer of 3 embryos intended; Patients who have had more than 3 transfers or more than 6 embryos replaced without pregnancy or puncture rank> 3; uterine malformation existing; Presence of a hydrosalpinx.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 38 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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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Natural cycle<br>Ovulation is not induced by drugs | Other: natural cycle<br>* Ovulation is not induced by drugs<br>* Other names: natural;|
| Experimental: Moderate ovarian stimulation<br>Ovulation is induced by recombinant follitropin alpha and recombinant choriogonadotropin | Drug: moderate ovarian stimulation<br>* Ovulation is induced by recombinant follitropin alpha and recombinant choriogonadotropin<br>* Other names: ovarian stimulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of visits | number of visits (for clinical examination, ultrasound and hormonal dosage) required to monitor ovulation in both groups | From inclusion visit to embryo transfer : up to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fertiqol | the score of quality of life related to the couple's infertility, the Fertiqol questionnaire, a questionnaire validated by the European Society of Human Reproduction and Embryology (ESHRE) and taking into account the tolerance to treatment; | From inclusion visit to embryo transfer : up to 90 days | 
| defrost cancellation rate | the defrost cancellation rate cycle started, whatever the cause: Early ovulation problem of organization, ... excluding non-transfer related to embryo lysis thawing | From inclusion visit to embryo transfer : up to 90 days | 
| transfer on weekends and holidays | the transfer rate on weekends and holidays | From inclusion visit to embryo transfer : up to 90 days | 
| HCG levels> 100 U / L | the incipient pregnancy rate per transfer defined by a HCG levels> 100 U / L | From inclusion visit to pregnancy test : up to 100 days | 
| pregnancy | the rate of pregnancy by ultrasound transfer defined by the presence of a cardiac activity | From pregnancy test to ultrasound at 6 week of gestation : up to 100 days | 
| Birth | The live birth rate per transfer defined by the birth of at least one living child | From transfer to delivery : up to 9 months | 
| Gestationnal age at delivery | the term of delivery | From transfer to delivery : up to 9 months | 
| Implantation | the implantation rate defined by the total number of live births to the total number of embryos replaced | From transfer to delivery : up to 9 months | 
| Miscarriage | the rate of early miscarriage (before 12 SA) | From pregnancy test to ultrasound at 6 week of gestation : up to 100 days | 
| Cost | the average estimated cost of drug treatment and monitoring (ultrasound and hormone assays). | From pregnancy test to ultrasound at 6 week of gestation : up to 100 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovulation Induction, quality of life, Reproductive Physiological Processes, fertility