Early pregnancy loss (EPL) refers to a nonviable pregnancy in the first trimester. The overall incidence of EPL ranges from 10% to 25% of all recognized pregnancies. Approximately 80% of all pregnancy losses occur in the first trimester.1,2 Following the diagnosis of an EPL, patients may experience depression and anxiety.3 They may also feel guilty or alone after their EPL, and some may even believe it was preventable.4 Patients in this vulnerable circumstance often want to know what they can do differently in future pregnancies to prevent a similar outcome. Counseling patients during this time is vital. In this article, we highlight the most common questions and counseling points that come up after a patient experiences EPL (Figure).
Takeaways
- Early pregnancy loss (EPL) counseling is crucial, and clinicians should take time to discuss these important topics with patients.
- No workup is indicated after a single EPL.
- Adherence to preconception low-dose aspirin can increase the chance of live birth after an EPL.
- Patients with a history of a prior pregnancy loss who experience vaginal bleeding in early pregnancy should be offered 400 mg of vaginal micronized progesterone twice daily.
- Patients can experience depression and anxiety after EPL and should be offered support.
Cause and recurrence
Often, patients are anxious to know why they had an EPL. Approximately 50% of EPL cases are associated with a chromosomal abnormality.5,6 This can be reassuring to patients, as most EPLs are sporadic abnormalities and thus unlikely to occur again. Although having an EPL is a risk factor for a subsequent loss, the actual risk of a second consecutive loss remains very low.1,7,8 In patients with an EPL, an estimated 5% will experience a second consecutive loss, and 1% will have 3 or more losses.9 A nonmodifiable risk factor for EPL is the patient’s age. An increased risk for EPL exists in patients with advancing maternal age, with the incidence increasing to 40% at age 40 and 80% at age 45. Therefore, for patients older than 40 years, it may be helpful to put into perspective their risk of EPL. Many other possible factors may influence EPL that are less common; these can include drug use (alcohol, tobacco, cocaine), maternal chronic diseases, obesity, acute maternal infections, certain medications, and reproductive tract abnormalities. Air travel, contraception use, exercise, prior abortion, sexual activity, and stress have not been found to be correlated with early pregnancy loss.10 It is important to highlight for patients that the most likely outcome will be a normal pregnancy after a single EPL. Counseling on modifiable risks such as maternal smoking can help patients optimize their chances of a live birth in their subsequent pregnancy.
Workup
Given that most EPLs occur due to a sporadic chromosomal abnormality and there is a low likelihood of a consecutive EPL, a workup is not recommended after a single occurrence.1 However, it is worthwhile letting patients know that if they do experience a subsequent loss, a workup would be initiated to try to understand the cause of their recurrent pregnancy losses.
Prevention
Patients often ask if there is anything they can do to prevent EPL from occurring in their next pregnancy and how to best optimize their health. In addition to routine preconception counseling, which can include genetic carrier testing as indicated or desired per patient preference, we will discuss if there are other interventions to offer patients.
Aspirin
Prophylactic antenatal aspirin use for patients at high risk for preeclampsia is well accepted as a preventive measure during pregnancy.11 There has been interest in learning if there is a benefit with aspirin use for EPL prevention. Aspirin may improve blood flow and reduce inflammation in reproductive organs, and if you start aspirin before conception it could improve endometrial growth and vascularization.12,13 To investigate preconception aspirin use in patients with a prior EPL, Schisterman et al conducted the EAGeR trial (NCT00467363). In this trial, they initially sought to recruit patients with 1 prior loss at less than 20 weeks to be randomly assigned to receive either preconception daily low-dose aspirin (81 mg) plus folic acid (treatment group) or placebo plus folic acid for up to 6 menstrual cycles.
Due to slow recruitment, the investigators expanded their study sites and participant criteria from only 1 prior loss to 1 or 2 prior pregnancy losses, including those at greater than 20 weeks’ gestation. When they assessed the groups, 58% (n = 309) of participants in the low-dose aspirin group had live births compared with 53% (n = 286) in the placebo group. They found there was no difference in live birth rates, with an absolute difference of 5.09% (95% CI, –0.84 to 11.02).13 However, when they looked at their original recruitment stratum (participants with 1 prior loss at less than 20 weeks’ gestation), 62% (n = 151) of participants taking low-dose aspirin had a live birth compared with 53% of participants taking placebo (n = 133; relative risk [RR], 1.17; 95% CI, 1.01-1.37). In this trial, the primary outcome of live birth rate did not show a difference in the expanded stratum; however, there was a higher live birth rate in patients with only 1 prior pregnancy loss who received baby aspirin vs placebo in their original stratum.
In 2021, Naimi et al published data from a post hoc analysis of the EAGeR trial considering participant adherence to treatment to determine whether there was an impact of preconception aspirin use on EPL.14 When looking at this population of 1227 patients, the investigators considered a patient to be adherent when they were taking aspirin for at least 5 of 7 days in the week for at least 70% of their time in the study. When adherence was used as a criterion for the aspirin use group, participants with 1 to 2 prior losses were found to have 6 fewer losses per 100 participants and 15 more live births per 100 in the adherent population than those taking placebo.14 The researchers also investigated the optimal time to initiate low-dose aspirin and found that the positive effect of aspirin on live birth was lower when aspirin initiation was delayed to 6 or more weeks’ gestation.
Taking these findings into account, you can counsel patients with 1 prior loss that preconception low-dose aspirin may reduce their risk of pregnancy loss and increase their chance of a live birth. However, initiation before conception, or as soon as possible after a positive pregnancy test, and adherence are important.
Progesterone
Progesterone is crucial to the support of a pregnancy and because of this, researchers have investigated whether giving supplemental progesterone can prevent EPL. The PRISM trial (ISRCTN14163439) was a randomized trial that investigated the impact of vaginal progesterone compared with placebo in pregnant women. Participants included those without a prior loss who were experiencing vaginal bleeding early on in their pregnancy. In this trial, the researchers did not find a difference in live birth rate when comparing the vaginal progesterone with placebo.15 However, in a predefined subgroup analysis they found that in patients with 3 prior EPLs, receiving vaginal progesterone increased the rate of live birth. A meta-analysis of 7 randomized trials involving 5682 women was conducted to estimate the effectiveness and safety of different progestin treatments for threatened and recurrent miscarriage.16 The data showed that in asymptomatic patients with recurrent miscarriage, vaginal micronized progesterone made little difference to live birth rate when compared with placebo.16 However, for patients with one or more previous EPLs experiencing bleeding in pregnancy, vaginal micronized progesterone increased the live birth rate compared with placebo (RR, 1.08; 95% CI, 1.02-1.15).
Based on this evidence, patients with a prior pregnancy loss who present with bleeding or signs of a threatened miscarriage may be offered micronized vaginal progesterone. However, without signs of bleeding or miscarriage, supplemental progesterone has not been found to increase the live birth rate. It is important to counsel patients who have experienced a loss that they would be eligible for progesterone therapy if they experience bleeding early on in a subsequent pregnancy.
Vitamin supplementation
Balogun et al undertook a review of 40 trials to assess if vitamin supplementation given prior to 20 weeks’ gestation impacted EPL. The trials evaluated vitamin C, vitamin A, multivitamins, folic acid, and antioxidant vitamins. The investigators found that there was no difference in risk of EPL with any of the vitamin supplementation. The only difference they noted was a decreased stillbirth rate in patients who received multivitamins containing both iron and folic acid.17 Although vitamin supplementation is recommended and beneficial for fetal well-being, it has not been shown to reduce a patient’s risk of EPL.
Conceiving again
Patients may wonder when it is safe to try again for pregnancy after experiencing an EPL. Retrospective data suggest there are no differences in neonatal outcomes when comparing patients who tried immediately after EPL with those who delayed conception.18,19 To better understand this, researchers conducted a secondary analysis of the EAGeR trial.
In this study, 1000 women with EPL were prospectively followed, and subsequent pregnancy outcomes were recorded. Women who attempted to conceive within 3 months of their pregnancy loss (n = 765; 76.7%) were able to achieve a live birth within a significantly shorter time (OR, 1.71; 95% CI, 1.30-2.25) than women who waited more than3 months (n = 233; 23.4%).20 Fifty-three percent delivered a live birth in the 0 to 3–month group compared with 36.1% in the group that waited more than 3 months before attempting to conceive. Participants in the 0 to 3–month group were slightly younger, had a lower body mass index (BMI), were more likely to be never-smokers, and less likely to report subfertility. However, after adjusting for age, race, BMI, education, and subfertility, women with a 0 to 3–month vs greater than 3–month intertrying interval had a shorter time to pregnancy (OR, 1.58; 95% CI, 1.25-2.00) and shorter time to pregnancy leading to a live birth (OR, 1.71; 95% CI, 1.30–2.25). Researchers in this study also saw no differences in pregnancy risks or outcomes between the 2 groups. Given these data, it is reasonable to counsel patients that it is safe to start trying when they are emotionally ready and that there may be a shorter time to pregnancy and higher live birth rates if they try sooner.
Resources and support after EPL
Following an EPL, patients can experience significant depression and anxiety and can report feeling guilty or alone.3 In a national survey, results indicated that only 45% of patients felt they received adequate emotional support from the medical community.21 In data from a qualitative study of patients who had a previous EPL, participants reported that therapy and in-person support groups are helpful, and these are highly requested when patients are experiencing an EPL.21 Participants also felt that support from a peer who had also experienced an EPL was extremely valuable.
These data highlight a clear area of improvement for clinicians treating patients with EPL. We know that patients experience grief, depression, and anxiety and can feel alone. We also know that patients are not often being offered any emotional support from the medical community, even though they believe it would be helpful to receive support. Clinicians should identify local support groups for patients and highlight the potential benefit of talking to friends and family who may have experienced an EPL.
References
1. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin No. 200: early pregnancy loss. Obstet Gynecol. 2018;132(5):e197-e207. doi:10.1097/AOG.0000000000002899
2. Wang X, Chen C, Wang L, Chen D, Guang W, French J. Conception, early pregnancy loss, and time to clinical pregnancy: a population-based prospective study. Fertil Steril. 2003;79(3):577-584. doi:10.1016/s0015-0282(02)04694-0
3. Farren J, Mitchell-Jones N, Verbakel JY, Timmerman D, Jalmbrant M, Bourne T. The psychological impact of early pregnancy loss. Hum Reprod Update. 2018;24(6):731-749. doi:10.1093/humupd/dmy025
4. Bardos J, Hercz D, Friedenthal J, Missmer SA, Williams Z. A national survey on public perceptions of miscarriage. Obstet Gynecol. 2015;125(6):1313-1320. doi:10.1097/AOG.0000000000000859
5. Stephenson MD, Awartani KA, Robinson WP. Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case-control study. Hum Reprod. 2002;17(2):446-451. doi:10.1093/humrep/17.2.446
6. Alijotas-Reig J, Garrido-Gimenez C. Current concepts and new trends in the diagnosis and management of recurrent miscarriage. Obstet Gynecol Surv. 2013;68(6):445-466. doi:10.1097/OGX.0b013e31828aca19
7. Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 2012;98(5):1103-1111. doi:10.1016/j.fertnstert.2012.06.048
8. Nybo Andersen AM, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ. 2000;320(7251):1708-1712. doi:10.1136/bmj.320.7251.1708
9. Stirrat GM. Recurrent miscarriage. Lancet. 1990;336(8716):673-675. doi:10.1016/0140-6736(90)92159-f
10. Prine LW, MacNaughton H. Office management of early pregnancy loss. Am Fam Physician. 2011;84(1):75-82.
11. ACOG Committee Opinion No. 743: low-dose aspirin use during pregnancy. Obstet Gynecol. 2018;132(1):e44-e52. doi:10.1097/AOG.0000000000002708
12. Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res. 2003;110(5-6):255-258. doi:10.1016/s0049-3848(03)00379-7
13. Schisterman EF, Silver RM, Lesher LL, et al. Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial. Lancet. 2014;384(9937):29-36. doi:10.1016/S0140-6736(14)60157-4
14. Naimi AI, Perkins NJ, Sjaarda LA, et al. The effect of preconception-initiated low-dose aspirin on human chorionic gonadotropin-detected pregnancy, pregnancy loss, and live birth : per protocol analysis of a randomized trial. Ann Intern Med. 2021;174(5):595-601. doi:10.7326/M20-0469
15. Coomarasamy A, Devall AJ, Cheed V, et al. A randomized trial of progesterone in women with bleeding in early pregnancy. N Engl J Med. 2019;380(19):1815-1824. doi:10.1056/NEJMoa1813730
16. Devall AJ, Papadopoulou A, Podesek M, et al. Progestogens for preventing miscarriage: a network meta-analysis. Cochrane Database Syst Rev. 2021;4(4):CD013792. doi:10.1002/14651858.CD013792.pub2
17. Balogun OO, da Silva Lopes K, Ota E, et al. Vitamin supplementation for preventing miscarriage. Cochrane Database Syst Rev. 2016;2016(5):CD004073. doi:10.1002/14651858.CD004073.pub4
18. Goldstein RR, Croughan MS, Robertson PA. Neonatal outcomes in immediate versus delayed conceptions after spontaneous abortion: a retrospective case series. Am J Obstet Gynecol. 2002;186(6):1230-1236. doi:10.1067/mob.2002.123741
19. Vlaanderen W, Fabriek LM, van Tuyll van Serooskerken C. Abortion risk and pregnancy interval. Acta Obstet Gynecol Scand. 1988;67(2):139-140. doi:10.3109/00016348809004186
20. Schliep KC, Mitchell EM, Mumford SL, et al. Trying to conceive after an early pregnancy loss: an assessment on how long couples should wait. Obstet Gynecol. 2016;127(2):204-212. doi:10.1097/AOG.0000000000001159
21. Conroy C, Jain T, Lin T, Mody SK. Assessing interest in a peer support person for patients experiencing early pregnancy loss: results from a national survey. Womens Health Rep (New Rochelle). 2024;5(1):268-275. doi:10.1089/whr.2023.0132
