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October 16, 2023
Pregnancy and Infant Loss Awareness Month
Human Chorionic Gonadotropin for Miscarriage Prevention: A Review of Research
By: Kaitlyn Chantrey
Director’s Note: To mark Pregnancy and Infant Loss Awareness Month, we are featuring research that assessed the effectiveness of human chorionic gonadotropin (hCG) to prevent recurrent miscarriage. The study[1] was summarized by Kaitlyn Chantrey, a former FACTS elective participant. Published in 2013 by Morley et al, the study lends insight into maternal risk factors and treatment options for couples who experience unexplained recurrent miscarriage. Fertility awareness-based methods (FABMs) may be a valuable diagnostic tool for these couples. Women who chart their cycles are often able to identify pregnancy earlier, which may facilitate more timely interventions and enable more accurate capture of data about the miscarriage. To learn more, you may also read the research related to miscarriage conducted by our executive director, Dr. Marguerite Duane, as part of her fellowship at the University of Utah under the mentorship of Dr. Joe Stanford.
Introduction
Miscarriage is both a devastating and relatively common occurrence on a woman’s journey to grow her family. Fifteen to twenty percent of all pregnancies end in miscarriage, defined as loss of pregnancy before 20 or 24 weeks gestation.[1][2] The potential for recurrent pregnancy loss rises with every miscarriage a woman experiences. A woman is classified as having recurrent miscarriages if she experiences 2 to 3 or more miscarriages in her lifetime.[1][2] This affects 1 to 3% of all couples who conceive and remains poorly understood once other risk factors have been eliminated. Miscarriage rates are affected by systemic maternal conditions such as poorly controlled diabetes, other endocrine disorders, lupus, coagulation disorders, and obesity. Environmental disruptors such as smoking, alcohol, caffeine, and certain medications can also have a significant role in pregnancy. For half of women, the reason for recurrent miscarriage is unknown.
One treatment approach to potentially reduce the rate of miscarriage is supplemental human chorionic gonadotropin (hCG), a glycoprotein hormone secreted by the syncytiotrophoblast cells of the placenta. This hormone prompts the corpus luteum to increase progesterone and estradiol, helping maintain the pregnancy. Through its effect on the corpus luteum, hCG is also thought to play a role in endometrial function.
“One treatment approach to potentially reduce the rate of miscarriage is supplemental human chorionic gonadotropin (hCG), a glycoprotein hormone (that) prompts the corpus luteum to increase progesterone and estradiol, helping maintain the pregnancy.”
The study by Morley et al[1] summarized below was designed to evaluate the effectiveness of using hCG to prevent recurrent miscarriage of unknown cause. The study group was compared to a control trial in which the women obtained no additional medical intervention.
Methodology
This study used multiple prior studies to collect their data. Two blinded review authors evaluated studies for methodology quality and inclusion assessment. A third review author was recruited in case agreement could not be settled on data quality between the two review authors, but was not needed.
Five randomized controlled trials (RCTs) were collected from the Cochrane Pregnancy & Childbirth Group’s Trials Register after meeting the following criteria: hCG used for prevention (not management), unexplained prior miscarriages, and no IVF patients. Systemic disease screening, immunological and endocrine assays, bacterial and viral testing, pelvic imaging, and chromosomal analysis were completed to rule out dependent risk factors.
Each study had individual dosing regimens that differed from the other studies; this was not considered in the analysis. A fixed meta-analysis was conducted for statistical analysis using the review manager software.
Results
Through the use of five combined studies in the meta-analysis, a total of 596 women with recurrent miscarriages were evaluated. When all five studies were analyzed, the results were statistically significant in terms of reducing the rate of miscarriage with hCG as an intervention (RR 0.51, CI 0.32-0.81). The number needed to treat was seven.
With the use of all five studies, there appeared to be statistical heterogeneity (I2= 39%). Two studies with the highest favor in support of hCG were also noted to be the oldest studies with the least power. When the data from these two studies were removed from the analysis, the findings were still favorable for hCG but no longer statistically significant (RR 0.74, CI 0.44- 1.23). The study affirmed the use of hCG was safe in pregnancy with none of the five studies reporting any adverse effects.
Discussion
While the use of hCG may prevent recurrent miscarriages, additional studies with more power are needed to ensure statistical significance. Nevertheless, hCG remains a potential treatment option for women at risk for recurrent miscarriage, especially since there were no adverse events to mother or baby associated with its use in the five studies analyzed.
“hCG remains a potential treatment option for women at risk for recurrent miscarriage, especially since there were no adverse events to mother or baby associated with its use in the five studies analyzed.”
Limitations for the study mainly stemmed from a reduced power due to a lower number of women who participated in the combined studies. Half of all women with recurrent miscarriages had a disease or extenuating factors that play a role in this condition; thus, they could not be included in the meta-analysis. The study further limited enrollment by excluding women pursuing IVF treatment.
Recurrent miscarriage is a challenging and disheartening adversary on a couple’s journey to grow their family, which makes this research highly relevant to the field of women’s health and family planning. Many couples report depression, isolation, and low self-esteem when they experience recurrent pregnancy loss. Its relatively common occurrence in the general population emphasizes the need for physicians to address both the mental health impact and different treatment options available to these couples.
“Recurrent miscarriage is a challenging and disheartening adversary on a couple’s journey to grow their family, which makes this research highly relevant to the field of women’s health and family planning.”
To further evaluate the use of hCG in recurrent miscarriage, a more solid understanding of the exact role hCG plays in implantation and endometrial function is still needed. Future studies also need a more standardized approach regarding hCG dosing regimens to enable comparisons between studies. Another useful addition would be to include anxiety and depression screenings as women enroll into future studies to assess and address the impact of miscarriage on mental health.
After excluding the older, lower-powered studies, this meta-analysis was unable to provide statistically significant evidence to support the use of hCG to prevent recurrent miscarriages. Despite this limitation, hCG remains a promising alternative for women and couples as we await more data to assess its full impact in maintaining a viable pregnancy.
References
[1] Morley LC, Simpson N, Tang T. Human chorionic gonadotropin (hCG) for preventing miscarriage. Cochrane Database Syst Rev. 2013;(1):CD008611. Published 2013 Jan 31. doi:10.1002/14651858.CD008611.pub2.
[2] Duane M, Schliep K, Porucznik CA, Najmabadi S, Stanford JB. Does a short luteal phase correlate with an increased risk of miscarriage? A cohort study. BMC Pregnancy Childbirth. 2022 Dec 9;22(1):922. doi: 10.1186/s12884-022-05195-9. PMID: 36482355; PMCID: PMC9733331.
ABOUT THE AUTHOR
Kaitlyn Chantrey
Kaitlyn Chantrey is a fourth-year medical student at Des Moines University College of Osteopathic Medicine. She grew up in the Chicago suburbs and completed her undergraduate training through the Iowa State College of Agriculture. She is pursuing residency in family medicine with special interests in rural practice, lifestyle medicine, and integrative medicine. She enrolled in the FACTS course to further educate herself on alternative contraceptive and fertility treatments to offer patients that do not require the use of exogenous hormones.