Impact of Corpus Luteum Presence or Absence in the Incidence of Preeclampsia After Frozen Embryo Transfer

Study Overview
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Brief Summary
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Identifying modifiable factors that contribute to preeclampsia risk associated with assisted reproduction can improve maternal health. Recent studies have shown an increased risk for hypertensive disorders of pregnancy after in vitro fertilization, particularly for pregnancies occurring during a hormone replacement therapy such a donor egg recipient and a frozen embryo transfer. This risk may be partly attributable to the degree by which the assisted reproductive treatment affects the maternal hormonal environment, when the corpus luteum is a major source of reproductive hormones. On the other hand, cryopreserved embryos are usually thawed and replaced in in a natural or hormonally manipulated cycle; on this point, frozen embryo transfer is associated with better perinatal outcome regarding preterm birth and low birth weight yet higher risk of large for gestational age and macrosomia compared to fresh transfer. The objective of our study is to investigate whether the absence of corpus luteum adversely affects pregnancy and to analyse if there are differences in the perinatal outcomes due to differences in the endometrial preparation protocol for a frozen embryo transfer.

Official Title
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Impact of Corpus Luteum Presence or Absence in the Incidence of Preeclampsia After Frozen Embryo Transfer

Conditions
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Pre-Eclampsia, Frozen Embryo Transfer

Intervention / Treatment
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* Procedure: FROZEN EMBRYO TRANSFER IN SUBSTITUTED CYCLE


Participation Criteria
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Eligibility Criteria
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Inclusion criteria All patients who, after IVF-PGT-A treatment with their own oocytes, present a euploid embryo for transfer. Transfer of a single euploid embryo Exclusion criteria: Moderate or high smoking (> 5 cigarettes/day) BMI ≥30 kg/m2 Chronic hypertension History of preeclampsia in previous pregnancies History of delayed uterine growth and placental insufficiency in previous pregnancies Use of donor sperm Woman's age ≥44 years Women with menstrual cycles longer than 35 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 44 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized prospective analysis.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: FROZEN EMBRYO TRANSFER IN NATURAL CYCLE<br>After confirming ovarian rest (follicles < 10 mm) with menstruation by means of vaginal ultrasound, an ultrasound control of the natural cycle will be carried out, inducing ovulation when an ovulatory follicle of size ≥ 17mm and an endometrium ≥ 7mm are found. Serum estradiol and progesterone values will be determined that day. This induction will be carried out with an ampoule of 250 μg of rHCG (Ovitrelle®). After the injection of Ovitrelle®, the administration of micronized vaginal progesterone (Progeffik® or Utrogestan®) 200 mg/ 12 hours and 7 days after the injection, thawing and transfer of a frozen euploid blastocyst will begin 48 hours later. | |
| Active Comparator: FROZEN EMBRYO TRANSFER IN SUBSTITUTED CYCLE<br>After confirming ovarian rest (follicles < 10 mm) with menstruation by vaginal ultrasound, hormone replacement therapy with oestrogens (6 mg/day of oral oestradiol valerate - Progynova® or Progyluton®- or 150 ug/48 h of oestradiol in patches - Evopad®) will be started on day 2-3 of the cycle. On day 10-15 of treatment an ultrasound scan will be performed to assess endometrial growth and ovarian rest. After confirming an endometrial thickness ≥ 7mm by vaginal ultrasound, ovaries with follicles smaller than 10 mm, blood estradiol >100 pg/ml and serum progesterone < 1 ng/ml, luteal phase support will begin with the administration of 400 mg of micronized vaginal progesterone every 12 hours, a total of 10 shots, prior to embryo transfer of a thawed euploid blastocyst. same day. If the level of serum progesterone on the day of transfer is less than 9.2 ng/ml, a daily injection of subcutaneous progesterone (Prolutex®) will be added on the same day. | Procedure: FROZEN EMBRYO TRANSFER IN SUBSTITUTED CYCLE<br>* The intervention group will be prepared with hormone replacement therapy with estrogens according to usual clinical practice. Frozen embryos will be transferred after ten doses of exogenous progesterone.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of pre-eclampsia during pregnancy. | Presence or absence of pre-eclampsia during pregnancy | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding during pregnancy | Presence or absence of Bleeding during pregnancy | 12 months | 
| Hypertension during pregnancy | Presence or absence of Hypertension during pregnancy | 12 months | 
| Eclampsia during pregnancy | Presence or absence of Eclampsia during pregnancy | 12 months | 
| Preeclampsia during pregnancy | Presence or absence of Preeclampsia during pregnancy | 12 months | 
| Retarded intrauterine growth during pregnancy | Presence or absence of retarded intrauterine growth at birth | 12 months | 
| Premature detachment of normoinserted placenta during pregnancy | Presence or absence of premature detachment of normoinserted placenta during pregnancy | 12 months | 
| Type II Diabetes during pregnancy | Presence or absence of Type II Diabetes during pregnancy | 12 months | 
| Help Sindrome during pregnancy | Presence or absence of Help Sindrome during pregnancy | 12 months | 
| Alterations in the volume of the amniotic fluid during pregnancy | Presence or absence of alterations in the volume of the amniotic fluid during pregnancy | 12 months | 
| Preterm premature rupture of membranes during pregnancy. | Presence or absence of preterm premature rupture of membranes during pregnancy | 12 months | 
| Fetal death | Presence or absence of fetal death at birth. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pre-Eclampsia, Corpus Luteum, Frozen embryo transfer, Endometrial preparation