O-318 Decline of βhCG concentrations following pregnancy loss: exploring contributing factors
Authors: Juuel E , Schlaikjær Hartwig T , Guldborg Johnsen M , Bliddal S , Friis Petersen J , Herskind N  R , Vinterberg N  M , Rørbæk Kamstrup P , Westergaard D , Svarre Nielsen H 
Published: July 2024

Abstract

Study question
Which factors impact βhCG decline after a pregnancy loss, thereby inhibiting return of menstrual cycle?

Summary answer
In pregnancy loss, decline in βhCG levels are influenced by gestational age, BMI, previous losses, and treatment method, impacting menstrual cycle resumption.

What is known already
Despite one in four pregnancies ending as a pregnancy loss, there is limited knowledge about when to expect reproductive recovery including the decline in βhCG. The placentally produced hormone βhCG binds to luteinizing hormone/hCG-receptors, which, through negative feedback in the pituitary, decreases release of gonadotropins. This limits chances of ovulation, thus inhibiting the onset of menstrual bleeding, however with great individual variability. Therefore, there is an unmet need for a more individualized understanding of the impact of maternal factors on the decline in βhCG concentrations and the relationship between βhCG and reproductive recovery after a pregnancy loss.

Study design, size, duration
The Copenhagen Pregnancy Loss study (COPL) is a prospective cohort focusing on pregnancy loss.

Participants/materials, setting, methods
Inclusion criteria required diagnosis of missed, spontaneous or anembryonic miscarriage and hCG results from both day of inclusion and follow-up visit 4-8 weeks later. Primary objective end points were serum-hCG on day of the diagnosis of pregnancy loss and at follow-up. Secondary end points from the follow-up visit included information on return of menstruation. Per laboratory protocol, βhCG &gt; = 5 IU/L is indicative of pregnancy. Analysis was done using a multivariable Bayesian ordinal regression model.

Main results and the role of chance
Preliminary results, to be updated for presentation at ESHRE 2024: 1,306 women were included in this study between November 2020 - January 2024. Follow-up visits were conducted 6 weeks after pregnancy loss (IQR: 5.6-7.0 weeks). At follow-up, 199 (18.0%) women still had elevated concentrations of βhCG.
At the time of pregnancy loss, gestational age (OR: 0.97, 95% CI 0.96-0.98), BMI (OR: 0.98, 95% CI 0.96-0.99), and number of prior pregnancy losses (OR: 1.09, 95% CI 1.01-1.18) were associated with βhCG.
βhCG concentration, measured at the follow-up, was strongly influenced by the choice of treatment method, including surgical (OR: 2.74, 95% CI 1.76-4.26) and medical (OR: 1.69, 95% CI 1.11-2.56), compared to spontaneous. Furthermore, Age (OR: 1.02, 95% CI 1.00-1.04) and gestational age (OR: 1.01, 95% CI 1.00-1.01) also affected the decline. βhCG levels at follow-up were correlated with return of menstrual bleeding OR: 0.98, 95% CI 0.96-0.99). Of the women with βhCG levels exceeding 5 IU/L, 145 out of 199 (72.9%) reported the resumption of their menstrual cycle. Among those with βhCG levels above 25 IU/L, 17 out of 33 (52%) reported menstrual cycle return.

Limitations, reasons for caution
Analysis depicted total-hCG concentrations (intact hCG + free ß-subunit) without distinguishing between the various hCG isoforms. The cohort was gathered at a hospital, reflecting that setting.

Wider implications of the findings
Our findings are the first step towards a more personalised approach for patients facing pregnancy loss, aiding with counselling and planning of reproductive prospects, including IVF. The evident ßhCG-induced negative feedback, coupled with menstrual bleeding in women with elevated ßhCG, highlights system complexity and hints at additional unidentified factors.

Trial registration number
not applicable