Effect of Miscarriage on Future Pregnancies

“…loss of a pregnancy causes great distress to couples and undermines their confidence in achieving future reproductive success.”

Miscarriages occur in 12–15% of all clinically recognised pregnancies [1]. However, early loss of a pregnancy causes great distress to couples and undermines their confidence in achieving future reproductive success. To date, clinical attention has mainly centered around the management of recurrent pregnancy loss, which is known to have an adverse effect on subsequent pregnancies. By contrast, a single miscarriage has not traditionally been perceived as a major clinical problem. It is rarely life threatening, its diagnosis and management is usually straightforward, and any prejudicial effect on future reproductive potential remains unproven.

“Despite their rarity, the effects of recurrent miscarriages on subsequent reproductive outcomes have dominated the literature. Relatively little is known about the consequences of a single miscarriage on future reproductive health.”

Research into the reproductive consequences of miscarriage presents a number of challenges. The first involves criteria for the diagnosis of the clinical entity itself. The current definition of miscarriage as spontaneous loss of pregnancy before 24 weeks of gestation (fetal weight <500 g) has been strongly influenced by advances in neonatal intensive care and notions of perceived viability. Problems with ascertainment and recall bias present a second challenge. Most data on miscarriage are derived from hospital episodes and therefore exclude cases occurring at home. Self-reported cases of miscarriage in population-based surveys are susceptible to reporting bias [2]. Third, epidemiological studies of outcomes following miscarriage are limited by the absence of an ideal comparison group. In terms of future obstetric events, neither parous women nor women in their first pregnancies are comparable with women with a previous miscarriage. Women with a previous termination of pregnancy at a similar gestational age may provide a suitable comparison group, but data on abortion are difficult to obtain, and many databases do not distinguish between spontaneous and induced abortions.

Recurrent miscarriages occur in 1% of women. Despite their rarity, the effects of recurrent miscarriages on subsequent reproductive outcomes have dominated the literature. Relatively little is known about the consequences of a single miscarriage on future reproductive health. Reproductive outcomes following miscarriage can include no further pregnancies, miscarriage or ectopic pregnancy, termination of pregnancy, or ongoing pregnancy beyond 24 weeks resulting in either live birth or stillbirth. In the section below we consider each of these situations.

Effect of miscarriage on future fertility

Following the loss of a wanted pregnancy, most women are likely to keep trying until a live birth is achieved. Thus, the chances of conception following a miscarriage should be higher than those following a live birth. In a cohort of 261 women followed up for 6 years after a miscarriage, natural conception occurred in 97.7% of those without known fertility problems [3]. Another study reported that the pregnancy rate at 12 months was 76.2% in women discontinuing contraception [4]. The slightly reduced pregnancy rates in the second study may be explained by the shorter duration of follow-up and nonexclusion of women prone to subfecundity owing to advanced age, obesity or other lifestyle factors. A study involving Saudi Arabian women found a conception rate of 81.3% at 4 years, with 75.2% pregnancies occurring within the first year [5]. Maternal age had a strong influence on pregnancy rates, which were 90% in women under the age of 20 years, as opposed to 63.5% in women aged over 35 years.

Effect of miscarriage on subsequent pregnancy loss

A previous miscarriage is known to increase the likelihood of a subsequent pregnancy loss. In 1938, mathematical modeling by Malpas estimated the risk of recurrence to be 73% [6]. While the risks for recurrence reported by subsequent researchers have been lower, they remain markedly higher than that in control women. Stirrat coined the phrase ‘recurrent miscarriage’ to describe three or more consecutive miscarriages occurring in the same woman [7]. Although initially an epidemiological concept based on a review of existing literature, the term ‘recurrent miscarriage’ has since dominated the clinical literature. As a clinical entity it enjoys a prominence in terms of the need for formal investigations and management denied to the more common ‘sporadic’ or isolated miscarriage.

There are few data on the risks of ectopic pregnancy or induced abortion after miscarriage. Hassan and Killick reported higher odds of ectopic pregnancy following miscarriage [4]. In addition, a previous live birth prior to the miscarriage enhances the likelihood of an induced termination. Despite reports of increased rates of termination for congenital anomalies, induced abortion following miscarriage is less common than after either a previous live birth or an induced termination of pregnancy.

Effect on a subsequent ongoing pregnancy

Over 70% of women who miscarry in their first pregnancy are destined to carry a subsequent pregnancy beyond 24 weeks. However, as yet relatively little is known about the potential complications in this second pregnancy. An extensive search of the literature identified four publications. Of these, two focused exclusively on the effects of second trimester miscarriage [8,9], while one was unable to distinguish between spontaneous and induced abortion [10]. Nevertheless, all produced remarkably consistent findings. The risks of preterm birth and perinatal death were increased in women with a previous miscarriage and were markedly higher in cases of late miscarriage. Other complications that were inconsistently shown to be more common in these women include pre-eclampsia [11] and bleeding in early pregnancy [12]. These data need to be interpreted with caution since sample sizes for most of these studies, (especially those limited to second trimester miscarriage) are small, resulting in wide confidence intervals. In a recently published study we examined the effects of a single miscarriage on a subsequent continuing pregnancy [13]. We found that women with a previous miscarriage were prone to adverse perinatal outcomes in the next pregnancy in comparison with; a) women who had a successful first pregnancy; and b) women with no previous pregnancies. Women with a previous miscarriage were at higher risk of threatened miscarriage and preterm delivery. They were more likely to have interventions during labor and delivery and their babies tended to be small for their gestational age. However, despite evidence of statistical significance in terms of relative risks, the absolute risks of adverse perinatal outcomes were low.

Effect of recurrent miscarriage

There are a number of publications regarding the risks of pregnancy complications following recurrent miscarriage, often reporting conflicting results. Reginald et al. found increased rates of preterm delivery, small for gestational age babies and perinatal deaths in pregnancies following recurrent miscarriage [14]. Hughes et al. found these rates to be no higher than that in the control population [15]. More recent studies have reported higher risks of preterm delivery, growth retardation and perinatal mortality [16,17]. The risk of preterm delivery appears to be a consistent finding in pregnancies following miscarriage and tends to show a dose-dependent rise in incidence [18].

Effect of maternal age on pregnancy outcomes

Advanced maternal age has been consistently shown to affect pregnancy outcomes [19]. Age has a profound effect not only on future pregnancy outcome, but also on fertility itself [4,5]. On the other hand, increasing the interpregnancy interval following a miscarriage appears to improve perinatal outcomes in the next pregnancy. A report of a WHO technical consultation on birth spacing recommends delaying the next pregnancy for a minimum of 6 months following a miscarriage or abortion in order to optimize outcomes. This recommendation was based on the findings from a single large Latin American study, which found that abortion–pregnancy intervals of less than 6 months were associated with increased risk of preterm birth and growth restriction [20]. By contrast, a retrospective case series based in California found no evidence of adverse neonatal outcomes associated with conceptions immediately following a miscarriage [21]. Ultimately, the adverse effects of advancing age should be balanced against delaying subsequent pregnancies and advice should be tailored to the needs of individual women.

Investigating women after miscarriage: clinical options

At present, existing guidelines in the UK make a clear distinction between the management of sporadic and recurrent miscarriages. While no investigations are currently recommended after one or two miscarriages [101], three miscarriages appears to be the threshold for initiating investigations to determine the cause of miscarriage [102]. Such a policy does not take into account maternal age, previous infertility or chromosomal make-up of the conceptus (where available).

The reason for such an approach is unclear, but is likely to be informed by economic considerations. In a National Health Service setting, the cost implications of investigating all women after a single miscarriage are likely to be prohibitive. There are two possible alternative strategies. The first, although not specified in the guidelines, is often practiced in many early pregnancy units. Investigations for recurrent miscarriage are considered following two consecutive miscarriages if the female partner is above the age of 35 years. The second option is based on a classification of recurrent miscarriage suggested by Dawood et al. [22]. Extending their classification to include sporadic miscarriages, miscarriages are classified as:

• Pre-embryonic or embryonic. These occur before 8 weeks of gestation and are often due to karyotypic or immunological abnormalities. Investigations should include karyotyping;

• Early fetal losses. Occurs between 8–12 weeks of gestation. These are often associated with antiphospholipid syndrome or thrombophilia and appropriate investigations are recommended to confirm the diagnosis;

• Late fetal loss or spontaneous second trimester losses. These should be investigated for the presence of anatomical abnormalities of the uterus and cervix. Investigations to rule out bacterial vaginosis should be carried out in women with a history of preterm rupture of membranes.

In this way, it is possible to develop an algorithm of investigations specific to the timing and perhaps the cause of miscarriage.

Conclusion

Experience of one or more previous miscarriages can increase the risks in a subsequent pregnancy. Fortunately for most women, absolute risk of future complications remains low. However, this does suggest the need for greater vigilance in the next pregnancy and obstetric surveillance of women should not be restricted to those with recurrent miscarriage.