Frozen Embryo Transfer, Hormone Replacement Therapy, Dydrogesterone, Infertility, Female
Conditions
Brief summary
To investigate the efficacy of dydrogesterone 30 mg compared to micronized vaginal progesterone 800 mg daily for luteal phase support in hormone replacement therapy frozen embryo transfer cycles, as confirmed by visualization of fetal heart activity by pelvic ultrasound assessment of ongoing pregnancy at 12 weeks of gestation.
Detailed description
A randomized controlled trial comparing dydrogesterone 30 mg versus micronized vaginal progesterone 800 mg daily for luteal phase support in hormone replacement therapy frozen embryo transfer cycles. Patients will undergo an embryo transfer in a hormone replacement therapy cycle using Progynova 2 mg three times daily until an endometrium thickness of at least 7 mm is reached. Afterwards two different luteal phase supplementation methods will be compared. The primary outcome of the study is ongoing pregnancy at 12 weeks of gestation. We will also investigate other prenatal and neonatal outcome factors as well as patients satisfaction and safety of dydrogesterone.
Interventions
10 mg three times daily
DRUGMicronized progesterone
2x 200 mg vaginal tablets two times daily
Sponsors
CRG UZ Brussel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label randomized controlled trial
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* ≤40 years of age at the time of IVF/ICSI treatment * BMI ≥18 to ≤30 kg/m2 with a documented history of infertility * Have undergone COS as part of an ART treatment and have had an unsuccessful fresh embryo transfer in that cycle, OR, have undergone freeze all strategy * Scheduled to undergo FET with a standard exogenous/programmed hormonal replacement therapy (HRT) regimen * Have at least 1 blastocyst vitrified on the 5th or 6th day after oocyte retrieval * Elective single embryo (blastocyst) transfer (SET) * Normal ultrasound examination at enrollment (or if \<12 months old) * Signed patient authorization for use/disclosure of data.
Exclusion criteria
* Women with a history of recurrent miscarriage, defined as \>2 consecutive miscarriages (biochemical pregnancy losses are not included) * Absence of implantation (serum hCG = negative) after two consecutive cycles of IVF, ICSI or FET where the cumulative number of transferred embryos was \>4 cleavage-stage embryos and \>2 blastocysts * Presence of hydrosalpinx that is not surgically treated * Endometrial abnormalities on scanning during ovarian stimulation, such as endometrial polyp(s), sub mucosal fibroid(s), endometrial hyperplasia, endometrial fluid accumulation, or endometrial adhesions * Participating in another clinical study at the same time * Known allergic reactions to dydrogesterone or other progestogens products * Any contraindication or other condition that precludes use of dydrogesterone in a particular patient, in accordance with the precautions listed in the locally approved label * Mental disability or any other lack of fitness, in the Investigator's opinion, to preclude subjects in or to complete the study * History of prior chemotherapy * Contraindication for pregnancy * Transfer of \>1 embryo
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ongoing pregnancy | 12 weeks | visualisation of a fetal heart activity via pelvic (vaginal/abdominal) ultrasound examination at 12 weeks of gestation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of delivery | follow-up time of 30 days after delivery | time of delivery (gestational week) will be confirmed (by calculation from date of embryo transfer) |
| Incidence of Treatment-Emergent Adverse Events | follow-up time of 30 days after delivery | Tolerability and safety will be asses during the whole study period. Adverse events will be considered as unexpected if the nature, seriousness, severity or outcome of the reaction(s) is not consistent with the reference information. The expectedness of adverse events for the medications used in this study is detailed in the reference safety information in the current summary of product characteristics (SmPCs) issued in the participating countries. All serieus suspected unexpected serious adverse drug reactions (SUSARs) will be subject to expedited reporting. The investigator is responsible for submitting reports of SUSARs to the appropriate national regulatory authorities within the required reporting period. The investigator is responsible for notifying the IECs/IRBs in writing of the SUSARs within the required reporting timelines. Copies of the notification will be maintained by the investigator in the study documentation files. |
| Patient reported outcome | day 12-18 of luteal phase supplementation (pregnancy test) and at 12 weeks gestation | Questionnaire (using the Treatment Satisfaction Questionnaire of Medication (TSQM)) and recording information on treatment tolerability and convenience |
| Incidence of newborn adverse events | follow-up time of 30 days after delivery | Newborn wellbeing and safety including congenital malformations will be evaluated after delivery via a telephonic contact with the patient |
| Biochemical pregnancy rate | day 12-18 of luteal phase supplementation (pregnancy test) | serum hCG test (\> 25 mIU/ml), without ultrasound evaluation of a pregnancy |
| Clinical pregnancy rate | Day 33-39 of LPS (Verification of pregnancy) | assessed by transvaginal ultrasound and defined as the presence of ≥1 gestational sac on examination |
| Miscarriage rate | 22 weeks | defined as spontaneous loss of a clinical pregnancy before 22 weeks of gestation (where embryo(s) or fetus(es) is/are nonviable and is/are not spontaneously absorbed or expelled from the uterus) |
| Live birth rate | 22-42 weeks | as the birth of a live newborn after 22 weeks of gestation |
| Rate of pre-eclampsia | follow-up time of 30 days after delivery | Incidence of pre-eclampsia as defined by the defined as the development of hypertension after 20 weeks of gestation together with one or more new-onset conditions: proteinuria, maternal or uteroplacental dysfunctions. Univariate and multivariable regression analysis were performed to control for known or potential PE risk factors, more specifically: body mass index (BMI), African ethnicity, previous history of hypertensive disorders of pregnancy, mean arterial pressure (MAP) at the first prenatal consultation, polycystic ovary syndrome (PCOS) and ovulation disorders, endometrial thickness and oocyte recipients. |
| Occurence of antenatal bleeding, ultrasonographic abnormalities, gestational diabetes, cholestasis | follow-up time of 30 days after delivery | Occurence of antenatal bleeding, ultrasonographic abnormalities, gestational diabetes, cholestasis |
| Implantation rate | Day 33-39 of LPS (Verification of pregnancy) | assessed by ultrasound and defined as the number of gestational sacs per number of embryos transferred |
| Blastocyst development score | at the time of embryo transfer (visit 2: day 6 of luteal phase supplementation) | using the system developed by Gardner |
| Number of cryopreserved embryos | day of screening and enrollment | Number of cryopreserved embryos |
| Summary characteristics of the preceding controlled ovarian stimulation cycle | day of screening and enrollment | information on used stimulation medication, total dose of stimulation medication used, duration of stimulation medication, trigger medication |
| Rate of preterm birth | follow-up time of 30 days after delivery | Delivery before 37 weeks of gestation |
Countries
Belgium
Outcome results
None listed