Trial to Assess the Pattern of Use of REKOVELLE® in Women Undergoing In Vitro Fertilisation (IVF) or Intracytoplasmic Sperm Injection (ICSI) Procedures in Routine Clinical Practice

Study Overview
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Brief Summary
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Study designed to observe the usage patterns, efficacy and safety of REKOVELLE® in women naive to IVF and ICSI, undergoing their first Controlled Ovarian Stimulation (COS) treatment cycle with REKOVELLE® in routine clinical practice.

Official Title
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Nordics and Switzerland Prospective Multicentre Non-Interventional Observational Study to Assess the Pattern of Use of REKOVELLE® in Women Undergoing In Vitro Fertilisation (IVF) or Intracytoplasmic Sperm Injection (ICSI) Procedures in Routine Clinical Practice (NORSOS)

Conditions
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Controlled Ovarian Stimulation

Intervention / Treatment
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* Drug: REKOVELLE®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females aged 18 years or older at enrolment Who have never been treated with (naïve) in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment using fresh or frozen ejaculated sperm from male partner or sperm donor Who are prescribed REKOVELLE® for the first time, using the dosing algorithm-based on AMH test result and body weight to define the 1st cycle dose regimen with REKOVELLE® according to the approved label Who have been informed verbally and in writing about this trial content, signed the inform consent and who do not object to their data being electronically processed Exclusion Criteria: Currently participating in an interventional clinical trial in which any treatment or follow-up is mandated Women with a contraindication for prescription of REKOVELLE® treatment Hypersensitivity to the active substance or to any of the excipients Tumours of the hypothalamus or pituitary gland Ovarian enlargement or ovarian cyst not due to polycystic ovarian syndrome Gynaecological haemorrhages of unknown aetiology Ovarian, uterine, or mammary carcinoma Primary ovarian failure Malformations of sexual organs incompatible with pregnancy Fibroid tumours of the uterus incompatible with pregnancy Pregnancy and breast feeding Women who undergo ovarian stimulation for fertility preservation Women placed under judicial protection, guardianship, or supervision Women who are considered as vulnerable population

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| REKOVELLE®<br> | Drug: REKOVELLE®<br>* Subjects must be treated according to the routine clinical practice and REKOVELLE® must be prescribed in accordance with the terms of the marketing authorisation of each participating country. According to the label the REKOVELLE® dose should be based on a recent determination of body weight and a recent determination of Anti-Müllerian Hormone (AMH) (i.e. within the last 12 months) measured by the following diagnostic tests: ELECSYS AMH Plus immunoassay from Roche or alternatively the ACCESS AMH Advanced from Beckman Coulter or LUMIPULSE G AMH from Fujirebio.<br>* Other names: follitropin delta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Use of the algorithm-based individualized dosing regimen (daily dose of REKOVELLE® administered) | Calculated with body weight and AMH serum level to define the daily dose of REKOVELLE® | Up to day 1 of REKOVELLE® stimulation | 
| Daily dose of REKOVELLE® |  | From day 1 up to day 20 of REKOVELLE® stimulation | 
| Number of days of treatment with REKOVELLE® |  | From day 1 up to day 20 of REKOVELLE® stimulation | 
| REKOVELLE® Dose changes | Dose changes is the discretion of the investigator | From day 1 up to day 20 of REKOVELLE® stimulation | 
| Use of the Algorithm dosing Application | Use of the Ferring developed dosing app for the daily dose calculation by answering yes/no | Up to day 1 of REKOVELLE® stimulation | 
| Use of GnRH protocol for Lutenizing Hormone surge suppression | Defined as a choice between GnRH agonist and GnRH antagonist | Up to day 10 | 
| Type of drug used for triggering of follicle maturation | Defined as a choice between hCG or GnRH | Between Day 8 and Day 14 | 
| Luteal phase support | Type and the length of luteal phase support is the discretion of the investigator. Decided as a choice between Progesterone, Oestrogen and hCG | 24-72 hours after oocyte-retrieval | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of ongoing pregnancy (≥1 intrauterine viable fetus 10-11 weeks after embryo transfer) in the fresh cycle |  | 10-11 weeks after embryo transfer | 
| Rate of ongoing pregnancy (≥1 intrauterine viable fetus 10-11 weeks after embryo transfer) following the fresh cycle, including also the first frozen embryo transfer |  | 10-11 weeks after embryo transfer | 
| Number of oocytes retrieved |  | Following 1st cycle with REKOVELLE® (each cycle range is 5-20 days, average 9 days) at 34-36 hours | 
| Number of oocytes/embryos/blastocysts frozen |  | Following 1st cycle with REKOVELLE® (each cycle range is 5-20 days, average 9 days) after oocyte retrieval | 
| Number of embryos/blastocysts transferred |  | Following 1st cycle with REKOVELLE® (each cycle range is 5-20 days, average 9 days) after oocyte retrieval | 
| Quality of fresh embryos or blastocysts transferred (excellent, good, fair, other) |  | Following 1st cycle with REKOVELLE® (each cycle range is 5-20 days, average 9 days) after oocyte retrieval | 
| Positive signs of pregnancy (clinical pregnancy) | Clinical pregnancy defined as least one gestational sac. | Following 1st cycle with REKOVELLE® (each cycle range is 5-20 days, average 9 days) Up to 5-6 weeks after embryo transfer | 
| Positive signs of pregnancy (Positive Human chorionic gonadotropin (hCG) test or urine pregnancy test) |  | Following 1st cycle with REKOVELLE® (each cycle range is 5-20 days, average 9 days) Up to 10-11 weeks after embryo transfer | 
| Pregnancy loss in women with embryo/blastocyst transfer (biochemical pregnancy, spontaneous/elective abortion, ectopic pregnancy, vanishing twin) | Biochemical pregnancy is defined as positive beta hCG (βhCG) test but no gestational sac is observed on later transvaginal ultrasound, or menstruation is reported. 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. Elective abortion is defined as induced abortion done at the request of the woman for other than therapeutic reasons. Ectopic pregnancy is defined as extrauterine gestational sac with or without fetal heart beat as documented by ultrasound or surgery. 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 embryo transfer | 
| Cycle cancellation before or after oocyte pick-up and reason for cycle cancellation | Date when the investigator decides to cancel cycle 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, OHSS, subject choice, other) | At consultation visit where cycle cancellation decided up to 10-11 weeks after embryo transfer | 
| Adverse drug reactions (ADRs) | Adverse drug reactions (ADRs) defined by the investigator | During 1st cycle with REKOVELLE® (each cycle range is 5-20 days, average 9 days), Up to 10-11 weeks after embryo transfer. | 
| Ovarian hyperstimulation syndrome (OHSS) (including mild/moderate/severe) | OHSS defined by the investigator (including mild/moderate/severe) | During 1st cycle with REKOVELLE® (each cycle range is 5-20 days, average 9 days), Up to 10-11 weeks after embryo transfer. | 
| Preventive interventions for early OHSS | Preventive interventions decided by the investigator (Triggering of final follicular maturation with GnRH agonist and fresh embryo/blastocyst transfer or cryopreservation, Cancellation of fresh embryo/blastocyst transfer) | During 1st cycle with REKOVELLE® (each cycle range is 5-20 days, average 9 days), Up to 10-11 weeks after embryo transfer. | 
| Assessment of overall subject experience and convenience with REKOVELLE® by the Subject Questionnaire (assessed by the subject) |  | 34-36 hours after final injection of 1st cycle with REKOVELLE® (average 9 days) |