Clinical trial NCT05167812: On Pregnancy After Losses - OPAL Study
Official title: On Pregnancy After Losses; Predicting Pregnancy Success in Couples With Recurrent Pregnancy Loss
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Recurrent Pregnancy Loss
Keywords: Prediction
Prognosis
Live birth
Pregnancy success chance
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2021-12-22
Enrollment: 1931
Sex: ALL
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Couples with RPL who have visited or will visit an "early pregnancy unit" or "RPL outpatient clinic" of the Leiden University Medical Centre (LUMC), Erasmus Medical Centre (EMC) or Amsterdam University Medical Centre (Amsterdam UMC) from 2006 onwards.

Brief summary: Rationale:

Recurrent pregnancy loss (RPL) is defined as the loss of two or more conceptions before the fetus reaches viability. It affects 1-3% of all fertile couples and despite extensive diagnostic work-up, in only around 30% an underlying cause is identified. Several factors may increase the risk for miscarriage, but the chance of a normal, successful pregnancy is still high. So, in supporting couples with RPL, an important part of the clinical management of these couples is to provide couples with accurate prognoses for their next pregnancy. The main limitation in current prediction models is the lack of a sufficiently large cohort, adjustment for relevant risk factors such that prognoses are individualized, and separating between the cumulative live birth rate and the chance that the next conception will lead to a live birth. In this project therefore we aim to make an individualized prognosis regarding the future chance of live birth and the chance of a healthy child. This could then lead to improved wellbeing and the ability of making future reproductive choices.

Objectives:

Primary objective: to predict the chance of a live birth within three years after intake in couples with unexplained RPL

Secondary objectives:

* to predict the chance of an ongoing pregnancy (\>12 weeks) in the next pregnancy in couples with unexplained RPL.
* to predict the chance of a complicated pregnancy in couples with unexplained RPL
* to predict the chance dynamically of a live birth given the outcome of a pregnancy after intake
* to predict the chance of above outcomes in couples with a known cause for RPL

Study design: A multicenter retrospective and prospective cohort study.

Study population:

Couples with females aged ≤42 years in both prospective and retrospective inclusion.

Retrospective inclusion: Couples with RPL who visited the RPL outpatient clinic in participating centers from 2006 until the start of this study.

Prospective inclusion: new couples with RPL who will visit the clinic from 2021 onwards.

Main study parameters/endpoints:

* Pregnancy outcomes since intake
* Time to pregnancy since intake
* Time between pregnancies since intake
* Pregnancy complications since intake
* All outcomes will be obtained up to a maximum of five years after intake
* Patient characteristics: cause for RPL, female age, male age, previous live birth, duration of RPL (since diagnosis)

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Participating in this study does not yield any risks. There could be a burden in case of retrospectively collecting data. Participating does not yield direct benefits for the subjects, however it may lead to future improvements of care for couples with RPL.


Eligibility criteria: Inclusion Criteria:

Couples that fulfill the following criteria are included (according to the ESHRE Recurrent Pregnancy Loss Guideline 2017):

* RPL in the current relationship: defined as the loss of ≥ 2 preceding pregnancies. These pregnancy losses include:

  * all pregnancy losses before the 24th week of gestation verified by ultrasonography or uterine curettage and histology
  * non-visualized pregnancies (including biochemical pregnancy losses and/or resolved and treated pregnancies of unknown location), verified by positive urine or serum hCG
  * both consecutive and non-consecutive pregnancy losses
* Dutch or English speaking couple
* Couples with females aged ≤42 years at intake

Exclusion Criteria:

* Mental or legal incapability of either the male or female of the couple
* Loss of \< 2 pregnancies in current relationship

Primary outcomes:
measure: Live birth of RPL couples within three years assessed by ultrasound or hCG after intake at the RPL clinic
timeFrame: 3 - 5 years
Secondary outcomes:
measure: Pregnancy outcomes since intake (miscarriage, ongoing pregnancy, live birth) assessed by ultrasound, hCG, or "take home baby"
timeFrame: 3 - 5 years
measure: Time to pregnancy since intake measured in days
timeFrame: 3 - 5 years
measure: Time between pregnancies since intake measured in days
timeFrame: 3 - 5 years
measure: Pregnancy complications since intake as registered by gynecologist or midwife
timeFrame: 3 - 5 years
Other outcomes:
Locations:
Study officials:
References:
citation: Youssef A, van der Hoorn ML, van Eekelen R, van Geloven N, van Wely M, Smits MAJ, Mulders A, van Lith JM, Goddijn M, Lashley E. Development of the OPAL prediction model for prediction of live birth in couples with recurrent pregnancy loss: protocol for a prospective and retrospective cohort study in the Netherlands. BMJ Open. 2022 Sep 23;12(9):e062402. doi: 10.1136/bmjopen-2022-062402.