The relationship between Caesarean section and subfertility in a ...

Human Reproduction Vol.17, No.7 pp. 1914–1917, 2002

The relationship between Caesarean section and subfertility in a population-based sample of 14 541 pregnancies D.J.Murphy1,3, G.M.Stirrat1, J.Heron2 and the ALSPAC Study Team2 1Division

of Obstetrics and Gynaecology and 2Division of Paediatric and Perinatal Epidemiology, University of Bristol, Bristol, UK

3To

whom correspondence should be addressed at: Division of Obstetrics and Gynaecology, St Michael’s Hospital, Southwell Street, Bristol BS2 8EG, UK. E-mail: [email protected]

BACKGROUND: There has been a threefold increase in the rate of Caesarean section over the past 25 years. The long-term consequences of Caesarean section may include subsequent subfertility. METHODS: We investigated the relationship between Caesarean section and subfertility within a cohort of 14 541 pregnant women. RESULTS: A history of previous Caesarean section was associated with an increased risk of taking >1 year to conceive from the time of planning a pregnancy, adjusted odds ratio (OR) 1.53 [95% confidence interval (CI) 1.09, 2.14]. This association was stronger for women of parity 艌 2, adjusted OR 2.97 (95% CI 1.72, 5.10). Nulliparous women with a history of subfertility were at increased risk of delivery by Caesarean section, adjusted OR 1.56 (1.22, 2.00) and OR 2.33 (1.64, 3.30) for durations of >1 and >3 years respectively. CONCLUSIONS: These findings suggest a complex relationship between Caesarean section and subfertility where subfertility may both precede and be a consequence of Caesarean section. Key words: Caesarean section/population-based study/subfertility

Introduction The rate of Caesarean section has risen threefold in the past 25 years without any evidence of improved outcomes for the mother or baby (Department of Health, 1997). The causes of the increase in rate of Caesarean section are not well understood but among the suggested factors are fear of litigation, the high false positive rate of intrapartum fetal heart rate monitoring, and fear of damage to the maternal pelvic floor during vaginal delivery (Stirrat, 1998). A maternal history of subfertility has been associated with an increased risk of delivery by Caesarean section (Li et al., 1991; Venn and Lumley, 1993; Reubinoff et al., 1997; Dulitzki et al., 1998; Pandian et al., 2001). There has been little attention, however, to the consequences of Caesarean section and, in particular, whether there is any relationship between delivery by Caesarean section and subsequent subfertility. A review of the literature on reproductive history subsequent to Caesarean section showed a statistically significant reduction in the likelihood of having any subsequent pregnancy in four out of six studies (Hemminki, 1996). It was not possible in these studies to address whether the subfertility was voluntary or involuntary or to account for many potential confounding factors. Time to conception is a useful epidemiological marker of subfertility, although it has limitations because it fails to account for couples who do not conceive and can be subject to a number of sources of bias (Baird et al., 1986; Baird and Wilcox, 1986; Weinberg et al., 1994; Olsen et al., 1998). In addition, careful consideration needs to be given to potential medical, obstetrical, social and socio1914

economic confounding factors (Baird et al., 1986; Weinberg and Wilcox, 1998; Ford et al., 2000). The aim of this study was to explore the relationships between Caesarean section and subfertility among women who planned a future pregnancy. Materials and methods The Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) has collected detailed information on the current and previous pregnancies of 14 541 women recruited from the Avon Health area between April 1991 and December 1992 (85% of the total eligible) (Golding, 1990). We examined the relationship between previous Caesarean section and the time interval to planned conception among women who had previously delivered a liveborn child. Of the 14 541 women recruited, 5787 (40%) had a previous liveborn child and 4006 of these had a planned pregnancy. The woman’s status in relation to previous Caesarean section and duration of trying to conceive was known in 3994 subjects. We also examined the relationship between a history of subfertility and subsequent delivery by Caesarean section among the 3435 nulliparous women (24%) who had planned pregnancies. The present study is based on information collected by self-completion questionnaires from each woman and her partner, at 18 weeks gestation and also following delivery. Specific fertility information included previous obstetrical and gynaecological history, sexual experience, oral contraception including duration of use, duration of cohabitation, paternity, whether the pregnancy had been planned and how long the parents had been trying to conceive. Other factors of interest included age of mother and her partner at the time of conception, their ethnic origins, highest educational level, the woman’s body mass index (BMI ⫽ wt/ht2), © European Society of Human Reproduction and Embryology

Caesarean section and subfertility

Table I. Relationship between previous Caesarean section and subsequent subfertility Subfertility

⬎1 year ⬎ 3 years

Total subfertile

306 59

Caesarean section

Odds ration (95% CI)

Previous n ⫽ 422 (%)

No previous n ⫽ 3572 (%)

Unadjusted n ⫽ 3994

Adjusteda n⫽ 3994

50 (11.8) 11 (2.6)

256 (7.2) 48 (1.3)

1.74 (1.26, 2.40) 1.97 (1.01, 3.81)

1.53 (1.09, 2.14) 1.70 (0.83, 3.47)

aAdjusted

for co-habitation, duration, oral contraceptive pill use, cigarette exposure, alcohol consumption, educational level, ethnicity, parity, change of partner and maternal body mass index (BMI). CI ⫽ confidence interval.

cigarette exposure, alcohol exposure and parity. Subfertility was defined at two levels, trying to conceive for ⬎1 year and for ⬎3 years. Subfertility has traditionally been defined as failure to conceive after 12 months, therefore 1 and 3 year time periods were selected for the original questionnaires to reflect short- and long-term subfertility. The mode of delivery was self-reported and cross-checked with the STORK maternity database. Parous women who had a previous Caesarean section were compared with parous women who had no previous Caesarean section at the two subfertility levels. The associations between previous Caesarean section and subfertility were further evaluated for the influence of parity. Caesarean section rates were compared between nulliparous women who had a previous history of subfertility and nulliparous women with no history of subfertility. Results are presented as unadjusted and adjusted odds ratios (OR) and 95% confidence intervals (CI) calculated by logistic regression using SPSS (version 10.0). Factors were included in the multivariable model based on a statistically significant difference between the two groups in the univariable analyses (P ⬍ 0.05) or if there was a biologically plausible potential for confounding. For our sample of 3994, the confounders used suffered from between 0 and 12% missing data. The method of creating an additional category denoting missing information was used when appropriate. There did not appear to be any relationship between the amount of missing data and our subfertility outcome (as one might expect) and restricting the sample to the completely observed cases (n ⫽ 3240) made little difference to the size of effect or width of CI.

Results A history of previous Caesarean section was associated with an increased risk of taking ⬎1 year to conceive from the time of planning a pregnancy [OR 1.74 (1.26, 2.40)] (Table I). The risk remained significant after controlling for maternal and paternal age at conception, co-habitation duration, oral contraceptive pill use, cigarette exposure, alcohol consumption, educational level, ethnicity, parity, change of partner and maternal BMI adjusted. Maternal and paternal age at conception had no additional effect on fertility after controlling for cohabitation duration and have been removed from the final model, adjusted OR 1.53 (1.09, 2.14). The factors included in the final model are important contributors to baseline fertility (Weinberg et al., 1994; Sallmen and Luukkonen, 2001). There was an increased risk of taking ⬎3 years to conceive following Caesarean section but the association did not reach statistical significance, possibly due to smaller numbers. The greatest increase in risk of subfertility following Caesarean section appears to be for women of higher parity (艌2), adjusted OR

2.97 (1.72, 5.10) and 2.37 (0.70, 8.04) for durations of ⬎1 and ⬎3 years respectively (Table II). This was confirmed by testing for a significant interaction. A P-value of 0.006 was obtained for the 1 year subfertility outcome. Nulliparous women were significantly more likely to deliver by Caesarean section where there was a maternal history of subfertility, adjusted OR 1.56 (1.22, 2.00) and 2.33 (1.64, 3.30), for durations of ⬎1 and ⬎3 years respectively (Table III).

Discussion This study suggests important associations between subfertility and delivery by Caesarean section. Unlike previous studies it was possible to identify women with involuntary subfertility and to control for known epidemiological associations and biologically plausible confounding factors. The direction of causality for an association between subfertility and delivery by Caesarean section is complex. The previously reported association between maternal history of subfertility and subsequent delivery by Caesarean section is confirmed by this study (Li et al., 1991; Venn and Lumley, 1993; Reubinoff et al., 1997; Dulitzki et al., 1998; Pandian et al., 2001). It appears to be independent of maternal age, BMI, and educational level. The women in this sample represented all types of subfertility and both elective and emergency Caesarean sections. The current analysis is based on nulliparous women and is not confounded, therefore, by any previous obstetric experience. Previous studies have reported specific associations between subfertility, obstetric complications and Caesarean section (Venn and Lumley, 1993; Pandian et al., 2001) but others have reported a higher rate of Caesarean section without any increased risk of maternal or fetal complications (Li et al., 1991; Reubinoff et al., 1997). Maternal choice and obstetrical anxiety may be contributing to increased Caesarean section rates for this group of women and this area warrants further research. The observed association between previous Caesarean section and an increased risk of subsequent subfertility is more difficult to explain. It is possible that this association reflects a pre-existing history of subfertility which played some part in the indication for a previous Caesarean section, however, the association persists even after controlling for important contributors to baseline fertility. It is interesting to note that the association between Caesarean section and subsequent subfertility is stronger for women of higher parity. This would 1915

D.J.Murphy et al.

Table II. Relationship between previous Caesarean section and subsequent subfertility according to parity Subfertility

Parity ⫽ 1 n ⫽ 2852 Parity 艌2 n ⫽ 1142

Total subfertile

Caesarean section

Odds ration (95% CI)

Previous (%)

No previous (%)

Unadjusted

Adjusteda

185 (7.2)

1.19 (0.77, 1.88)

1.05 (0.66, 1.69)

⬎1 year

209

24 (8.5)

⬎3 years ⬎1 year

39 97

6 (2.1) 26 (18.7)

33 (1.28) 71 (7.1)

1.67 (0.69, 4.01) 3.02 (1.85, 4.93)

1.52 (0.58, 4.01) 2.97 (1.72, 5.10)

⬎3 years

20

5 (3.6)

15 (1.5)

2.46 (0.88, 6.87)

2.37 (0.70, 8.04)

aAdjusted

for co-habitation, duration, oral contraceptive pill use, cigarette exposure, alcohol consumption, educational level, ethnicity, parity, change of partner and maternal BMI.

Table III. Relationship between subfertility and risk of Caesarean section delivery in nulliparous women

Caesarean section Vaginal delivery

Caesarean section Vaginal delivery aAdjusted

Total

Conceived

n ⫽ 3435

艌1 year n ⫽ 553 (%)

⬍1 year n ⫽ 2882 (%)

Unadjusted

Adjusteda

458 2977

106 (19.2) 447 (80.8)

352 (12.2) 2530 (87.8)

1.70 (1.34, 2.17)

1.56 (1.22, 2.00)

Total

Conceived

n ⫽ 3435

艌3 years n ⫽ 191 (%)

⬍3 years n ⫽ 3244 (%)

Unadjusted

Adjusted

458 2977

53 (27.7) 138 (72.3)

405 (12.5) 2839 (87.5)

2.69 (1.93, 3.76)

2.33 (1.64, 3.30)

Odds ratio (95% CI)

for maternal age, cigarette exposure, alcohol consumption, educational level, ethnicity and maternal body mass index.

appear to be contradictory as women of higher parity (parity 艌2) are generally less likely to be affected by subfertility and an association with only one previous pregnancy (parity ⫽ 1) precludes a dilutional effect of an intervening normal pregnancy between the Caesarean section and the index pregnancy. However, the higher parity group includes women with two or more previous Caesarean sections and it may be that there is a cumulative effect of repeat Caesarean sections on the risk of subfertility. Alternatively, it may be that women of greater parity with one or more previous Caesarean sections have a higher background rate of subfertility which persists through successive pregnancies. Prospective studies evaluating successive pregnancies are required to shed further light on this complex relationship. The underlying mechanisms for an association between Caesarean section and subsequent subfertility are unclear and may relate to infection, adhesion formation or placental bed disruption, which in turn may be influenced by the indication for Caesarean section. These mechanisms seem plausible in the light of the associations between Caesarean section and subsequent ectopic pregnancy, placenta praevia and placental abruption (Hemminki and Merilainen, 1996). We have not addressed the indications for Caesarean section or specific intrapartum and post-partum complications and these factors warrant further research. It is also important that 1916

Odds ratio (95% CI)

potential associations between Caesarean section and other reproductive outcomes are considered. This study evaluates subfertility from the perspective of women who succeed in having an ongoing pregnancy and therefore may underestimate the true magnitude of association (Weinberg et al., 1994). It is possible that some women will choose not to have a further pregnancy or will fail to achieve any further pregnancy following Caesarean section. It is important that these and further additional outcomes such as miscarriage and ectopic pregnancy are fully evaluated. The questionnaires used for the study addressed subfertility of 1 and 3 year durations, which precludes month by month survival type analysis and the calculation of fecundability ratios. The 1 year threshold level is the traditional threshold for referral to specialist fertility services and provides useful clinical information; however, future studies should record data on months to conception in order to increase statistical power for detailed evaluation of potential associations (Baird et al., 1986; Weinberg et al., 1994). The findings of the present study are in agreement with previous studies in showing an association between a history of subfertility and subsequent Caesarean section. Further studies are warranted to confirm the new finding that Caesarean section may have a negative influence on future fertility. Reliable evidence on long-term consequences of Caesarean

Caesarean section and subfertility

section is essential if women are to be offered informed choice with regards to mode of delivery. The justification for higher Caesarean section rates among women with a history of subfertility warrants critical review in order to establish whether operative deliveries are clinically indicated or simply the result of parental and obstetrical anxiety. Acknowledgements We are extremely grateful to all the mothers who took part and to the midwives for their co-operation and help in recruitment. The whole ALSPAC study team comprises interviewers, computer technicians, laboratory technicians, clerical workers, research scientists, volunteers and managers who continue to make the study possible. We are also very grateful for the helpful comments provided by the reviewers of the manuscript. This study could not have been undertaken without the financial support of the Medical Research Council, the Wellcome Trust, the UK Department of Health, the Department of the Environment, and the National Institutes of Health, a variety of medical research charities and commercial companies. This particular set of analyses was funded by the BUPA Foundation. The ALSPAC study is part of the WHO initiated European Longitudinal Study of Pregnancy and Childhood.

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