1

Risk of miscarriage after previously induced abortion

Cindhya Sithiravel (V-10)

A Student Thesis ( V-2015)

The Medical Faculty of University of Oslo

Supervisor:

Prof.I.em. Babill Stray-Pedersen MD, Dr.med.

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List of contents:

Abstract 3

Introduction:

- Surgical induced abortion 4

- Medical induced abortion 5

- Miscarriage 6

Methods 9

Results:

- Risk of miscarriage after previous surgical termination 10

- Risk of miscarriage after previous medical termination 13

Discussion 14

Summary and conclusion 16

Reference list 17

Table 1 21

3

Abstract

Background: The risk of miscarriage is approximately 15 % of clinically recognized

pregnancies, most of them appearing in first trimester. Miscarriage is known to be a

distressing event in a woman’s life. Hence, it would be in the patients’ favor to find any

association which reduces the risk of miscarriage. On the other hand, it is estimated that 30 –

50 % of all women undergo at least one induced pregnancy termination in their lifetime,

making any link between miscarriage and induced termination important.

Objectives: The purpose of this literature review is to investigate if there is any increased

risk of miscarriage in women who previously have undergone induced abortion. This thesis

will review the impact both prior surgical and medical termination has on subsequent

pregnancies in terms of miscarriage.

Methods: The searching tools Pubmed, Sciencedirect, McMastersPluus and Cochrane

Library have been used. They have been non-systematically searched with the words:

prior induced termination, surgical termination, medical termination, spontaneous abortion,

miscarriage, pregnancy outcomes, reproductive outcomes and birth ouctomes.

Results: Fourteen articles were reviewed. Twelve were looking at the association between

surgical abortion and miscarriage and two at the association between medical abortion and

miscarriage. Three review articles and eleven original studies are included. Two of the review

articles conclude with increased risk of miscarriage after surgically induced abortion, while

six of the nine primary studies looking at the risk of miscarriage after surgical abortion state

increased risk. Of these six studies, two show increased risk of early miscarriage, two show

increased risk of late miscarriage and the rest two studies show increased risk of miscarriage

at non-specified gestational week. None of the two primary studies which looked at the

impact medical abortion has on the risk of miscarriage show any increased risk. In total, eight

of the fourteen studies conclude with increased risk of miscarriage after induced abortion.

Conclusion: It is suggestive that medically induced termination does not increase the risk of

miscarriage in the subsequent pregnancies. However, there is difficult to draw a firm

conclusion on the risk of miscarriage in women with prior surgically induced abortion based

on the findings in this thesis. The results are conflicting and inconclusive. Further research,

methodologically stronger, is needed to assess the risk.

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Introduction

The risk of miscarriage is around 15 %, most of them appearing in the first trimester(1).

Miscarriage is known to be a distressing event in a woman’s life. (2). Hence it would be in the

patients’ favor to find any possible evidence which reduces the risk of miscarriage.

Today up to 42 million abortions are performed each year. It is well known that almost 1/3 to

½ of all women undergo at least one induced abortion during their lifetime (3). Worldwide

estimation indicate that 28 of 1000 women per year experience induced abortion; half of these

abortions are classified as unsafe, generally referring to terminations caused by illegal

procedures (4). The rate and safeness of pregnancy terminations are important health

indicators of one community since it is highly influenced by socioeconomically patterns.

Africa has the highest rate of unsafe abortions, as much as 97% percent of the terminations is

estimated to be unsafe. Western countries have the lowest rate of both safe and unsafe

abortions. The rate of complications is determined by the procedures used to induce the

abortion and the level of quality of the health care system where the termination is

experienced. (4)

This thesis is mainly reviewing the terminations performed in the Western countries where it

is generally two types of procedures to induce abortion: surgically induced and medically

induced abortions. A brief description of these two methods follows.

Surgically induced abortion

Background Abortions induced through surgical methods are more invasive than medical

terminations. The different surgical techniques available are dilatation and curettage, vacuum

aspiration and hysterotomy. The following will describe each of the techniques. (3)

Surgical methods:

Dilatation and curettage: Cervix is dilated either with medical intervention or placing

laminaria (thin seaweed sticks which expand in the presence of body moisture) through the

vagina before inserting forceps or curette to remove the content in the uterus. Patient is in

general anesthesia. (3)

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Dilatation and electric vacuum aspiration: After cervix dilatation one cannula is inserted into

the uterus. Connected to an electronic vacuum aspirator the cannula will be able to suck out

the contents in the uterus. Patient is in general anesthesia. (3)

Manual vacuum aspiration: A hand-held vacuum syringe will evacuate the contents of the

uterus into the syringe by suction. Local anesthesia is commonly used. (3)

Hysterotomy: This is a method similar to caesarian section where an abdominal opening is

made to get straight into the uterus. The contents are directly removed from the uterus without

going through the vagina. Rarely used. (3)

Complications:

Surgical termination is shown to be safe, effective and with minimal complications when

done in the first trimester. It seems to be a link between the complication rate and the

gestational length, the longer the gestation, the more increase in complications we see. The

complications we may see are cervical laceration, uterine perforation, infection, hemorrhage

and incomplete removal of the fetus and placenta. (3)

Medically induced abortion

Background: Medical terminations get increasingly available throughout the world. This is a

non-surgical method of inducing abortion with the use of prostaglandins, anti-progestagens

and/ or methotrexate. This method is mostly used in first trimester terminations. Medical

termination with the use of prostaglandins was developed in the 1970s, later in the 80s anti-

progestagens became readily available and in 1993 methotrexate was introduced for the same

purpose. (5) In Sweden the method got available from the 90s, while Norway, Denmark and

Finland started using it after 2000. Nowadays there are several drugs in the market to induce

termination; they may be used alone or in combination.

Pathophysiology of the drugs:

Prostaglandins: Prostaglandins are inflammatory mediators and are known to soften the

cervix and cause uterine contractions. It can be used both orally and vaginally. The most

known type is called misoprostol. Misoprostol has a success rate of 61% for single dose and

93% for repeat doses at inducing complete abortions. (5)

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Anti-progestagens: Mifepristone, an anti-progestagen, acts by increasing the sensitivity to

prostaglandins in uterus and inhibiting the progesterone and glucocorticoid receptors in uterus

leading to breakdown of the maternal capillaries in the desidua, increased prostaglandin

synthesis and inhibition of prostaglandin dehydrogenase. Mifepristone is shown to give higher

abortion rate when given in combination with prostaglandins, more than 95 % efficiency at up

to 63 days of amenorrhea. (5)

Methotrexate: Methotrexate is a folic acid antagonist which is cytotoxic to the trophoblasts.

Used in combination with misopristol it is highly effective, leading to a 98% complete

abortion rate if misoprostol is administered 7 days after methotrexate.(5)

Sideeffects and complications:

Side effects of medical method are heavy bleeding, nausea, pain, vomiting and diarrhea.

Medical termination is found to give longer duration of post termination bleeding compared to

surgical procedures.

The most important, but rare complication of medically induced termination is failed abortion

where the fetus continues growing. (5)

Miscarriage

Definitions, symptoms and signs:

Miscarriage is defined as inevitable spontaneous fetal loss caused by natural causes before the

20th – 22th gestational week. Spontaneous abortion is a synonym to miscarriage. ICD10

classifies spontaneous abortion into three groups:

Complete spontaneous abortion

Incomplete spontaneous abortion

Missed spontaneous abortion

In the complete spontaneous abortion the products of conception are expelled completely out

of the uterus without any remaining.. If the patient has retained tissue in the uterus after

pregnancy loss the diagnosis of incomplete spontaneous abortion is to be applied. In the

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newest ICD10 missed spontaneous abortion is described as a condition of retention of an

abortus which has been dead for at least 4 weeks. (6)

A pregnancy loss can proceed clinically unnoticed the first weeks of gestation if the

pregnancy is not detected by an hCG test before the onset of the miscarriage. Signs of a

miscarriage can include vaginal spotting or bleeding, abdominal pain or cramping, and fluid

or tissue passing from the vagina, though a missed miscarriage can lack any signs and

symptoms.(6)

Epidemiology:

A study done on the incidence of spontaneous abortion with a high sensitivity hCG test

among women who tried to conceive detected a miscarriage rate of 22% before the pregnancy

was clinically detectable. The total incidence of miscarriage, including the clinically detected

ones were estimated to be 31% of the total of 198 identified pregnancies. (7)

Etiology:

There is ongoing research on a large scale of any risk factors associated with miscarriage.

Some of the possible risk factors mentioned in the literature are caffeine, obesity, alcohol,

maternal age, tobacco, autoimmune sykdom (cøliaki blir for snevert-selv om det sikkert er

riktig; diabetes, SLE …..er også risikofaktorer), fetal abnormalities, uterine anomalies,

infertility and earlier induced termination.

A large population based study from Denmark consisting of more than 600 000 women

concluded that there is high level of fetal loss in women in their late 30s or older. (8) On a

similar note a population based cohort study from 2005 found miscarriage to be moderately

increased in women with celiac disease ( Rate ratio 1,31 ; 95% CI (1,06 to 1,61) ). (9)

A meta-analysis from 2006 found significantly higher odds of miscarriage among the women

with BMI ≥ 25 compared to normal weight women and concluded that there may be an

association between high body mass index and miscarriage risk. (10) A systematic review

from 2011 concludes that obesity ( BMI ≥ 28) is associated with increased miscarriage rate in

women compared to non-obese women (OR: 1,31; 95% CI (1,18 to 1,46) ). Since the results

are considered preliminary the same review is asking for larger studies on this association to

verify the results. (11)

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When searching for fetal abnormalities / chromosome defects linked to miscarriage, most of

the recent studies which came up were done on recurrent miscarriages. This is believed to be

the case because the recurrence risk in sporadically occurring miscarriage is low (12) and

there are already many well established studies from the 80s and 90s which have shown the

link between miscarriage and fetal abnormalities. One such study from 1980 showed that 493

of 1000 spontaneous abortions were having abnormal chromosome constitution (13). Fetal

abnormality is one of the most well established risk factors of miscarriage. Another well-

known risk factor is uncorrected uterine anomalies. The increased risk of miscarriage in this

patient population is estimated to be 36 % in one study from 1991 (14). This study and a

literature review from 2004 found septate uteri to be the uterine anomaly with the highest

abortion rate (15 ).

Smoking is yet another risk factor associated with miscarriage. A systematic review and meta-

analysis conducted in 2013 found that both maternal smoking and secondhand smoking

during pregnancy increased the risk of miscarriage significantly (16).

Besides maternal BMI, maternal age, fetal chromosomal defects, uterine abnormalities and

smoking previous miscarriage and subfertility are well known risk factors for having

miscarriage. A study from 2000 found that subfertility defined as a delay of 1 year or more

before recognizable conception gave a significantly higher miscarriage risk compared to

fertile women. (17) A literature review from 2002 which has reviewed the present literature

assessing risk factors of miscarriage suggests that there is a higher risk of miscarriage among

the women who have experienced miscarriage before and that the risk increases with the

number of previous cases. (18) A large population based study from 2007 concluded the same

finding that the increase doubled after one previous miscarriage. The same study also found

that the increase in risk doubled for those who had taken more than a year to conceive

compared to those who took less than 3 months. (19)

The link between miscarriage and alcohol and caffeine remains inconclusive in systematic

reviews and needs further investigative methodically strong studies. (20, 21)

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Methods

MacMasters Plus, Pubmed, Science Direct and Cochrane were searched with these words:

prior induced termination, surgical termination, medical termination, spontaneous abortion,

miscarriage, pregnancy outcomes, reproductive outcomes and birth outcomes. Most of the

studies that assessed the association between induced abortion and spontaneous abortion were

included in this literature review. There were no exclusion criteria, both old and new studies

with different methodological approach, different surgical techniques and different gestational

age at termination have been included. In total 14 studies are reviewed.

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Results

Fourteen studies were reviewed. Nine primary studies and three review articles which also

included some of the primary studies assessed evaluated the association between surgically

induced abortion and miscarriage. Two primary studies looked at the impact medically

induced abortion has on miscarriage. Of the three reviews one shows increased risk of

1.trimester miscarriage after a prior induced abortion with vacuum aspiration, while one

shows increased risk of 2.trimester miscarriage after dilatation and curettage. One of the

reviews states no increased risk. As for the primary studies none show any increased risk of

miscarriage after medical abortion, two conclude with increased risk of 1.trimester

miscarriage after surgical abortion, two state increased risk of late miscarriage after surgical

abortion and one shows that there is increased risk of both early and late miscarriage in

women with multiple prior surgical abortion. There is one primary study which doesn’t

specify the gestational week of the miscarriage, but has shown that there is increased risk

when the interpregnancy interval is less than 3 months. In total six of the nine primary studies

looking at surgical abortions state increased risk of miscarriage, none of the two primary

studies looking at medical abortions show increased risk and two of the three review articles

conclude with increased risk of miscarriage after surgical abortion. These results are shown in

table 1. I will hereby briefly review the results of each study included in this thesis.

Risk of miscarriage after previous surgical induced abortion

A prospective study from the US published in 1979 ( Harlap. S), observing 31 197 pregnant

women has evaluated the impact induced abortion has on miscarriage. They found no

increased incidence of miscarriage among women who opted for induced termination in their

second pregnancy having one livebirth in their first pregnancy, but the risk of midtrimester

miscarriage was increased in nulliparous women who underwent induced abortion. The risk

increased with the number of induced abortions after adjusting for age, social and

demographic factors. However the relative risk became statistically insignificant for those

who underwent induced abortion after 1973 with gentler techniques (Before 1973:RR 3,27. CI

(1,72 – 6,23), after 1973: RR 1,42, CI ( 0,72 – 2,65) ). Almost all the terminations were done

in the first trimester and the technique of choice after 1973 was suction curettage with

laminaria dilatation which replaced instrumental dilatation used before 1973. This study thus

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concluded that there is no increased risk if the induced abortion is done with gentle

procedures. (22)

One retrospective case-controll study, also from the US ( Levin. A) published the year after

challenged the previous results and concluded that a history of multiple induced abortions is a

risk factor for subsequent pregnancy loss up to 28 weeks gestation. A total of 1312 women

were included in this study. (23)

A pregnancy cohort study from 2003 done in China has evaluated if there is any increased

risk of miscarriage after a first trimester surgical termination. This study was conducted

during a 5 years period, from 1993 to 1998, with 2891 pregnant women. The pregnant women

were enrolled in a cohort group consisting of pregnant women with prior induced termination

through vacuum aspiration and a reference group consisting of primigravida. The odds ratio

of miscarriage between these two groups was calculated to be 1, 55 (95% CI 1,08 – 2,23)

after controlling for the confounding factors . This study article concluded that having first

trimester termination through vacuum aspiration increased the risk of first trimester

miscarriage in the subsequent pregnancy, but not of second trimester miscarriage (24). This is

contradicting to the WHO report from 1979 which suggested that second trimester

miscarriage was more common in women who had a history of induced abortion compared to

primigravida. (25)

A Danish cohort study from 2000 consisting of 61753 women who were primigravidas in the

years 1980 to 1982, with 12-14 years follow up time studied the risk of having miscarriage

after induced abortion as a function of the interpregnancy interval ( time between the induced

abortion and the subsequent pregnancy). Their study showed that the risk of miscarriage after

prior first trimester termination is increased when the interpregnancy period is less than 3

months independent of the surgical method of use (OR=4´06, 95% C.I.=1´98± 8´31)). The

number of induced abortions and the gestational age when the termination was conducted was

found not to affect the risk. (26)

An American retrospective study published in 2002 has assessed the impact of second

trimester dilatation and evacuation on subsequent pregnancy outcomes, miscarriage being one

of those. Ninety-six subsequent pregnancies in 81 women following prior second trimester

dilatation and evacuation were identified and assessed. This study concludes that there is no

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increased risk of second trimester miscarriage after a previous second trimester dilatation and

evacuation. (27)

One similar American retrospective study published in 2007 and reviewing 114 subsequent

singleton pregnancies after prior dilatation and curettage found no difference in the incidence

of miscarriage compared to overall expected incidence found in the literature. (28)

A population based study consisting of 2364 pregnancies among women with one induced

abortion has been conducted in Finland over a period of 12 years (1989 to 2001). This study,

published in 2006, has investigated if prior induced abortion is an independent risk factor for

different pregnancy outcomes, miscarriage being one of those. They found a miscarriage rate

of 40, 2 % in the obstetric history of women who had a previous induced abortion. (29)

A study from 2005 done in the US has aimed at describing the obstetric outcomes in patients

with prior surgical abortion at ≥ 20 weeks gestation. The surgical method of choice was

dilatation and evacuation. 121 pregnancies in 89 women were included in this study and first

trimester miscarriages occurred in 13 of these patients which is 10, 3 % of the patient group.

There were no cases of fetal loss in the second trimester. (30)

An UK population based case-control study from 2007 looking at the risk factors for first

trimester miscarriage shows that women who underwent one prior induced termination had

increased risk (OR 1.72 (1.27–2.31)), this increase in OR disappeared in women who had

undergone two or more prior terminations. 603 cases and 6116 controls were included in this

study. The method of induced termination is not specified . (19)

An American review from 1982, reviewing 10 different studies, evaluating the impact of

vacuum aspiration termination on future child bearing concludes that there is no increased risk

of having second trimester spontaneous abortion after a prior first trimester termination

through vacuum aspiration. (31)

An article from 1990 reviewing the effect of induced abortion on future reproduction writes

that most studies have concluded that vacuum aspiration carries no increased risk of

spontaneous abortion, while dilatation and evacuation, which as opposed to vacuum aspiration

more commonly is done in second and not first trimester, is associated with significantly

increased risk of spontaneous abortion (32)

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The latest review article included in this literature review, an article from 2010 assessing 3

systematic reviews and 2 primary studies on the association between induced abortion and

miscarriage writes that no clear cut conclusions can be made from the reviewed papers as the

literature is conflicting. (33)

Risk of miscarriage after previous medical induced termination

A population based study from 2007 done in Denmark consisting of 11 814 pregnancies has

obtained information about the subsequent pregnancies in women who have undergone first

trimester medical termination. Risk of miscarriage is one of the outcomes which have been

analyzed. The risk is compared to women who have undergone surgical termination and not

women without any past history of termination. After adjusting for confounding variables the

risk of having spontaneous abortion was not found to be significantly increased. The total

percentage of miscarriage in the group of women with prior medical termination was

estimated to be 12,2 %. As previously mentioned in this literature review, the rate of

miscarriage in healthy women is ranged to be between 11-22 %. The percentage found in the

population study therefore doesn’t raise any concern. The authors’ conclusion is that there

was no evidence that first trimester medical termination increases the risk of miscarriage.

(34)

A French prospective case-control study published in 2009 has examined whether induced

abortion with misoprostol either in the first or second trimester is a risk factor for late abortion

in the following pregnancies. 245 cases consisting of women with singleton deliveries

between week 16 – 18 of gestation because of late miscarriage, preterm delivery or preterm

premature membrane rupture were compared to 490 controls consisting of women with

singleton deliveries after 37 weeks of gestation. 16, 3 % of the cases and 11, 5 % of the

controls had a past history of induced termination with misoprostol, either alone, with

mifepristone or for cervical ripening before dilatation and curettage. This study concludes that

their study can give some reassurance that there is no increased risk of subsequent miscarriage

after prior induced abortion with misoprostol. (35)

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Discussion

In my review I have looked at the impact surgical and medical abortion have on both early

and late miscarriage. There were two primary studies and one review article that showed

increased risk of 1.trimester miscarriage, two primary studies and one review article which

stated increased risk of 2.trimester miscarriage, while I didn’t find any increased risk of

miscarriage after medical abortion. The three review articles included did have some of the

primary studies I have looked at. Since medical abortion is a relatively new method there was

not many studies on that and I couldn’t find any review articles on that area, however both the

primary studies included have the advantage of being done in the later years, thus making

them reliable. Coming to the studies of surgical abortion my findings are sort of in agreement

with the review articles included in this thesis as my thesis also finds eight of the twelve

studies showing increased risk of miscarriage. Nevertheless, I find it difficult to state a firm

conclusion of increased risk after prior surgical abortion based on my findings since there are

many conflicting results and my included studies don’t consist of homogenous study groups

in terms of trimester of induced abortion, trimester of miscarriage and the methods used to

induce abortions. It seems clear that medical abortion is safe on future pregnancies, maybe

because all are done in the 1.trimester.

Reviewing the association between induced abortion and miscarriage is challenging since the

women who undergoes induced abortion is thought to naturally have a greater fertility

compared to those who experience miscarriage. On the other side both fecundity and early

miscarriage is methodologically difficult to measure that can lead to an underestimation of the

fertility among the women with higher rate of miscarriage. (36) A conflicting situation in

these studies is that for some women who have induced abortion their pregnancy would have

ended in a spontaneous abortion anyways. Since prior miscarriage is believed to be an

independent risk factor for future miscarriage and since women with induced abortion and

women with miscarriage is believed to be different groups in terms on fertility it makes it

important yet complicated to differentiate these two groups of women. It is hard to adjust for

these factors which in most cases remains unknown. There is also a possibility that many

women with mid-trimester miscarriages could be missed out if they opt for early induced

abortion.

Another problem that arises in this type of studies is the decision of when to include the

women in the study so that we don’t miss clinically undetectable miscarriages. In prospective

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studies which start in the first prenatal visit which normally happens to be in the second

trimester the women who had early miscarriage are already eliminated. (37)

There are also challenges in how to stratify the case and control groups included in studies

assessing the association between induced abortion and miscarriage. How to determine the

most comparable groups for getting the most unbiased results still remains undiscussed in

most of the literature described in this article. Most of the studies have compared nulliparous

women with one or more induced abortions to primigravida women, some have compared the

groups accordingly to their gravity. None of the groups would be completely comparable in

terms of fertility and risk factors, since a woman with one induced abortion is different to both

a primigravida, a nulliparous with prior miscarriage and a multigravida with one childbirth.

Confirmation of induced abortion through interviews in the old studies and in the new studies

in countries without accurate registrations through medical chords makes the studies rely fully

on the information from the patients, which could give biased findings.

.

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Summary and conclusion

Fourteen articles were reviewed. Five prospective studies, six retrospective studies and three

review articles are evaluated Twelve were looking at the association between surgical

abortion and miscarriage and two at the association between medical abortion and

miscarriage. Three review articles and eleven original studies are included. Two of the review

articles conclude with increased risk of miscarriage after surgically induced abortion, while

six of the nine primary studies looking at the risk of miscarriage after surgical abortion state

increased risk. Of these six studies, two show increased risk of early miscarriage, two studies

show increased risk of late miscarriage and two studies shows increased risk miscarriage with

non-specified gestational week. None of the two primary studies which looked at the impact

medical abortion has on the risk of miscarriage show any increased risk. In total, eight of the

fourteen studies conclude with increased risk after prior termination.

On the basis of the findings from these studies the conclusion of this literature review article

would hence be that having medical abortion is highly suggestive of no increased risk of

miscarriage in the subsequent pregnancies. The patients should be advised to wait minimum 3

months until the next pregnancy after a prior termination since short interpregnancy interval is

associated with increased risk of miscarriage. There seems to be a correlation between the

method used to terminate and the risk of subsequent miscarriage, the gentle and safe surgical

procedures used in the developed countries in the first trimester today seems not to affect the

miscarriage risk. More methodologically strong large-scale studies looking at the risk of

having miscarriage are desirable. No conclusion can safely be made of the impact surgical

termination has on the risk of having miscarriage in the subsequent pregnancies from the

studies included in this article.

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