Study to Assess the Design of Use of REKOVELLE® in Women Undergoing In Vitro Fertilisation or Intracytoplasmic Sperm Injection Procedures in Routine Clinical Practice

Study Overview
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Brief Summary
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The aim of the study is to explore how the individualized dosing regimen of REKOVELLE is used in routine clinical practice and to describe the effectiveness and safety of REKOVELLE under real-world conditions.

Official Title
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French Prospective Multicentre Non-Interventional Study to Assess the Design of Use of REKOVELLE® in Women Undergoing In Vitro Fertilisation or Intracytoplasmic Sperm Injection Procedures in Routine Clinical Practice

Conditions
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Controlled Ovarian Stimulation

Intervention / Treatment
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* Drug: Follitropin Delta


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females aged 18 years or older at enrolment Who are treated for IVF or ICSI treatment cycle using fresh or frozen ejaculated sperm from male partner or sperm donor Who are prescribed REKOVELLE for the first time and using the dosing algorithm to define the dose regimen: a previous cycle with REKOVELLE should not be allowed Who have been informed verbally and in writing about this study content and who do not object to their data being electronically processed. Exclusion Criteria: Participating in an interventional clinical trial in which any treatment or follow-up is mandated Women with a contraindication for prescription of REKOVELLE treatment Oocyte donors Women undergoing ovarian stimulation for fertility preservation Women undergoing their third or fourth attempt of IVF or ICSI for the current parental project. Subject non-affiliated to French Social Security Women placed under judicial protection, guardianship, or supervision

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Follitropin Delta<br>Treatment according to routine clinical practice. | Drug: Follitropin Delta<br>* The Intervention (solution for injection) is delivered with a pre-filled injection pen. The REKOVELLE dose will be based on a recent determination (within the last 12 months) of AMH (anti- müllerian hormone) measured by the ELECSYS AMH Plus Immunoassay.<br>* Other names: REKOVELLE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily dose of REKOVELLE administered (for naïve and non-naïve subjects) |  | At the end of the stimulation protocol (up to 30 days) | 
| Duration of treatment with REKOVELLE (for naïve and non-naïve subjects) |  | From first until last day of REKOVELLE treatment (up to 30 days) | 
| Use of the dosing App (for naïve and non-naïve subjects) |  | At visit when the daily dose of REKOVELLE is decided (up to 2 hours) | 
| Type of Gonadotropin-Releasing Hormone (GnRH) used (for naïve and non-naïve subjects) |  | At visit (up to 2 hours) during the REKOVELLE treatment period | 
| Duration of treatment with GnRH (for naïve and non-naïve subjects) |  | At the end of the ovarian controlled stimulation (up to 2 weeks) | 
| Treatment used for the triggering of follicle maturation (for naïve and non-naïve subjects) |  | At the last visit during the REKOVELLE treatment period (from 5 to 30 days) | 
| Treatment used for Luteal phase support (for naïve and non-naïve subjects) | Decided as a choice between Progesterone, Oestrogen and hCG | From start of REKOVELLE treatment until 10-11 weeks after embryo transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Ongoing Pregnancy (for naïve and non-naïve subjects) | Ongoing pregnancy is defined as at least one intrauterine viable fetus, 10-11 weeks after first fresh or frozen embryo/blastocyst transfer. | Up to 10-11 weeks after transfer | 
| Number of oocytes retrieved (for naïve and non-naïve subjects) |  | At visit (up to 2 hours) at 36 hours after completed REKOVELLE treatment | 
| Number of oocytes/embryos/blastocysts frozen (for naïve and non-naïve subjects) |  | At Day 3 after oocyte retrieval | 
| Quality of fresh or frozen embryos or blastocysts transferred (excellent, good, fair, other) (for naïve and non-naïve subjects) |  | At Day 3, 5 or 6 after oocyte retrieval | 
| Implantation rate (for naïve and non-naïve subjects) | Implantation rate is defined as number of intrauterine viable fetus after transfer divided by the number of embryos/blastocysts transferred. | Up to 10-11 weeks after transfer | 
| Positive human chorionic gonadotropin (hCG) test (for naïve and non-naïve subjects) | Proportion of subjects with positive hCG test. | Up to 10-11 weeks after transfer | 
| Clinical pregnancy rate (for naïve and non-naïve subjects) | Clinical pregnancy is defined as least one gestational sac. | Up to 5-6 weeks after transfer | 
| Incidence of biochemical pregnancy (for naïve and non-naïve subjects) | Biochemical pregnancy is defined as positive beta hCG (βhCG) test but no gestational sac is observed on later transvaginal ultrasound, or menstruation is reported. | Up to 10-11 weeks after transfer | 
| Incidence of spontaneous abortion (for naïve and non-naïve subjects) | Spontaneous abortion is defined as positive βhCG test but all intrauterine gestational sacs without fetal heart beat as documented by ultrasound, or there are no viable fetuses observed by ultrasound. | Up to 10-11 weeks after transfer | 
| Incidence of elective abortion (for naïve and non-naïve subjects) | Elective abortion is defined as induced abortion done at the request of the woman for other than therapeutic reasons. | Up to 10-11 weeks after transfer | 
| Incidence of vanishing twins (for naïve and non-naïve subjects) | Vanishing twin is defined as spontaneous disappearance of an intrauterine gestational sac with or without heart beat in a pregnancy where one viable fetus remains as documented by ultrasound. | Up to 10-11 weeks after transfer | 
| Incidence of ectopic pregnancy (for naïve and non-naïve subjects) | Ectopic pregnancy is defined as extrauterine gestational sac with or without fetal heart beat as documented by ultrasound or surgery. | Up to 10-11 weeks after transfer | 
| Proportion of subjects with cycle cancellation (for naïve and non-naïve subjects) | Cancellation could be done before oocyte pick up (due to poor ovarian response, excessive ovarian response, any illness which prevents oocyte collection procedure, subject not taking hCG injection at the correct time, subject choice, other) or after oocyte pick up (due to no oocytes collected, no oocytes fertilized, abnormal fertilization, abnormal embryo development, no embryo development, ovarian hyperstimulation syndrome (OHSS), subject choice, other) | Up to 10-11 weeks after transfer | 
| Type of gonadotropin used (previous cycle information for non-naïve subjects) |  | At baseline | 
| Dose of gonadotropin used (previous cycle information for non-naïve subjects) |  | At baseline | 
| Duration of treatment with gonadotropin (previous cycle information for non-naïve subjects) |  | At baseline | 
| Type of GnRH used (previous cycle information for non-naïve subjects) | Defined as a choice between GnRH agonist and GnRH antagonist | At baseline | 
| Duration of treatment with GnRH (previous cycle information for non-naïve subjects) |  | At baseline | 
| Treatment used for the triggering of follicle maturation (previous cycle information for non-naïve subjects) |  | At baseline | 
| Treatment used for Luteal phase support (previous cycle information for non-naïve subjects) | Decided as a choice between Progesterone, Oestrogen and hCG | At baseline | 
| Number of oocytes retrieved (previous cycle information for non-naïve subjects) |  | At baseline | 
| Number of embryos/blastocysts transferred (previous cycle information for non-naïve subjects) |  | At baseline | 
| Incidence of pregnancy loss in women with embryo/blastocyst transfer (previous cycle information for non-naïve subjects) | Pregnancy loss included biochemical pregnancy, spontaneous / elective abortion, ectopic pregnancy. | At baseline | 
| Proportion of subjects with OHSS including moderate/severe grade (previous cycle information for non-naïve subjects) | Each OHSS case will be classified as moderate or severe. | At baseline | 
| Proportion of subjects with preventive interventions for early OHSS (previous cycle information for non-naïve subjects) | Preventive interventions cover triggering of final follicular maturation with GnRH agonist and fresh embryo/blastocyst transfer or cryopreservation of oocytes/embryos/blastocysts, cycle cancellation, coasting. | At baseline | 
| Proportion of subjects with preventive interventions for early OHSS (for naïve and non-naïve subjects) | Preventive interventions cover triggering of final follicular maturation with GnRH agonist and fresh embryo/blastocyst transfer or cryopreservation of oocytes/embryos/blastocysts, Cycle cancellation, Coasting. | Up to 10-11 weeks after transfer | 
| Frequency of adverse drug reactions (ADR) (for naïve and non-naïve subjects) | An ADR is characterized by the causal relationship between REKOVELLE and the adverse event is at least a reasonable possibility. | From start of REKOVELLE treatment until 10-11 weeks after embryo transfer | 
| Monitoring of the REKOVELLE treatment (number and intents of each visit) (for naïve and non-naïve subjects) |  | From Day 1 up to the last day of REKOVELLE stimulation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Follicle Stimulating Hormone (FSH), Assisted Reproductive Technologies (ART), Follitropin Delta, REKOVELLE