A prospective self-controlled study of fertility after second-trimester prostaglandin-induced abortion

Efficacy of fetal-pelvic index

Volume 158 Number 5

7. 8.

9. 10.

for primary cesarean section. Obstet Gynecol 1978;52: 407. Colcher AE, Sussman W. A practical technique for roentgen pelvimetry with a new positioning. A1R 1944;51:207. Shepard M1, Richards VA, Berkowitz RL, Warsof SL, Hobbins 1C. An evaluation of two equations for predicting fetal weight by ultrasound. AM 1 0BSTET GYNECOL 1982;142:47. Woods CE. A principle of physics as applicable to shoulder dystocia. AM 1 0BSTET GYNECOL 1943;45:796. Gonik B, Stringer CA, Held B. An alternate maneuver

for management of shoulder dystocia. AM 1 0BSTET GvNECOL 1983;145:882. 11. Acker OB, Sachs BP, Friedman EA. Risk factors for shoulder dystocia. Obstet Gynecol 1985;66:762. 12. Modanlou HD, Dorchester WL, Thorosian A, Freeman RK. Macrosomia-maternal, fetal, and neonatal implications. Obstet Gynecol 1980;55:420. 13. Lazer S, Biale Y, Mazor M, Lewenthal H, Insler V. Complications associated with the macrosomic fetus. 1 Reprod Med 1986;31:501.

A prospective self-controlled study of fertility after second-trimester prostaglandin-induced abortion I. Z. MacKenzie, MD, and Anna Fry, SRN, SCM Oxford, United Kingdom One hundred forty women whose pregnancies were terminated in the second trimester with prostaglandins because of suspected fetal disease have been prospectively followed to assess their subsequent fertility. In six instances difficulties had been experienced in conceiving the pregnancy that was terminated. Since abortion 104 women have conceived, 97% within 24 months of abortion but in five instances after some delay. Only one woman had not succeeded in conceiving a wished-for pregnancy. There were no apparent differences in abortion management between those women readily conceiving and those in whom there was some delay, although termination because of chromosomal reasons or anatomic abnormalities was less commonly followed by another pregnancy as compared with those terminated for rubella or other viral infections. Reduced fertility after a late prostaglandin-induced abortion thus appears to be very infrequent. (AM J 0BSTET GYNECOL 1988;158:1137-40.)

Key words: Abortion, prostaglandins, fertility

Since the passing of the Abortion Act 1967 in England and Wales, more than 2 million pregnancies have been terminated. During the past 16 years many studies have reported the relatively low level of physical and emotional morbidity that occurs immediately after therapeutic abortion. The initial fears expressed about probable adverse effects of termination on subsequent pregnancy have now largely been dispelled. '· 3 By comparison, however, there is a relative lack of objective controlled data assessing the effect of elective abortion on future fertility. To avoid any possible unnecessary anxiety and in the anticipation of a high rate of fertility challenge, a group of women whose pregnancies were terminated for suspected fetal disease

From the Nuffield Department of Obstetrics and Gynaecology, john Radcliffe Hospital, Headington. Received for publication January 5, 1987; revised july 8, 1987; accepted November 18, 1987. Reprint requests: Dr. I. Z. MacKenzie, Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Headington, Oxford, United Kingdom OXJ 9DU.

have been followed up prospectively to compare their ability to conceive the pregnancy that was terminated with their ability to conceive a subsequent pregnancy. Patients and methods

Patients undergoing an elective abortion at 13 to 24 weeks' gestation within Clause 4 of the Abortion Act 1967 for verified or suspected fetal disease during the years 1973 to 1983 have been prospectively studied. For all patients permission was requested at the time of abortion to make contact at a later date as part of a larger study assessing possible delayed sequelae.' All pregnancy terminations were performed by the use of prostaglandins, as shown in Table I, which also shows the gestational age at which pregnancies were terminated. Prostaglandins were given extraamniotically as described by MacKenzie and Embrey5 and intra-amniotically either alone or in combination with a hypertonic solution as described by MacKenzie et al. 6 In eight cases the abortion procedure was initiated by intra-amniotic prostaglandins and augmented by an extra-amniotic injection because of prolonged 1137

1138 MacKenzie and Fry

May 1988 Am J Obstet Gynecol

Table I. Prostaglandin administration route and gestational age of pregnancies terminated Gestation (wk) Administration route

13

I

14

I

15

I

16

I

I

17

18

I

19

I

I

20

21

I

22

I

23+

Total

Intra-amniotic Extra-amniotic Vaginal

7

2 4

1 8 1

3 6

20 8

20 7 1

22 9 1

7 1

5

2

3 2

83 54 3

Total

2

7

6

10

9

28

28

32

8

5

5

140

T 35-39 T 40+

Total

Table II. Indication for termination and age at termination in 140 patients Age (yr) Feta/ disease I disorder

<19

Anencephaly Spina bifida Other anatomic abnormality False-positive diagnosis Trisomy 21 Other chromosome rearrangements X-linked diseases Biochemical diseases Maternal rubella infection Other viral infection

3

3

Total

9

2 1

r

20-24

10 13 2 I

2

I

25-29

13 7 5 1 2

I

30-34

8 6 I

1 3 1

2

8

3 9 2

2 7

36

43

27

Results

During the 11-year period studied, 140 women had a pregnancy terminated for proved or suspected fetal abnormality; six of these pregnancies (4.3%) had been conceived after investigation and treatment for subfertility. Table II illustrates the fetal condition diagnosed

ll

1 3 4

I

abortion times. The three women in whom prostaglandins were given vaginally were treated with pessaries of 15-methyl-prostaglandin2 • (3 mg) repeated every 3 hours until abortion was completed. Prophylactic antibiotics were not routinely given, and surgical evacuation for retained products was performed only after expulsion of the fetus and the placenta when the latter was assessed to be incomplete. The majority of patients were seen and examined 6 weeks after abortion, at which time the postabortion autopsy findings were discussed and advice was given about future contraception and conception. All patients were managed by staff members experienced in midtrimester abortion induced with prostaglandins. Details about subsequent pregnancies were obtained by personal questionnaires sent 18 months or more after the abortion• or by identification of patients seen at the Oxford Obstetric and Gynaecological Unit. General practitioners were contacted with inquiries about any subsequent pregnancies or referral for subfertility problems for patients for whom information was not otherwise available.

35 30

13

I

4 8 15 2 5 28 2

12

140

5 5

before termination and the patients' ages at that time; 45 were para 0, 79 were para 1 or 2, and 16 were para 3 or 4. Four pregnancies were terminated because of raised serum and amniotic fluid a-fetoprotein levels or abnormality found on ultrasound examination for which no demonstrable abnormality could be found at postabortion autopsy; all these cases occurred during the first 4 years of a-fetoprotein screening. At the time of the initial abortion, nine women were given antibiotics because pyrexia developed during or after the abortion procedure; in three of them there was clinical suspicion of intrauterine infection. Since termination, 105 patients have wanted to conceive and 104 (99%) have been successful. Five patients reported that they were slow to conceive, taking 10 to 19 months; three had attended a fertility clinic, one had a normal result of laparoscopy, and one was given clomiphene to induce ovulation. All six patients who had difficulty conceiving the pregnancy that was terminated have subsequently conceived without difficulty or delay; one woman had conceived her terminated pregnancy by in vitro fertilization and achieved the subsequent pregnancy by this method also. For the 99 patients who experienced no difficulty conceiving, the mean ( ± SD) abortion to conception interval was 9.7 ± 13.5 months, whereas in the five patients who were slow to conceive the abortion to conception interval was 17.8 ± 10.0 months. Altogether, 51% had conceived within 6 months of termination, 68% con-

Volume 158 Number 5

ceived within 12 months, and 97% conceived within 24 months. The remaining three patients conceived after 35, 64, and 113 months, respectively; none had any concern about possible subfertility, as each conceived within 6 months of trying. All nine patients who received antibiotics at the time of abortion conceived without any difficulty. The mean ( ± SD) induction to abortion interval for all 140 patients was 16.3 ± 9.3 hours, whereas for the 104 who have subsequently conceived it was 16.6 ± 9.6 hours and for the 36 not subsequently pregnant it was 15.4 ± 8.3 hours (p = NS, Student's t test). Altogether, of the 23 patients who took >24 hours to abort, 18 have subsequently conceived and five have not; in none of these 18 patients was there a delay in conceiving. There were no obvious differences between abortion method and management for those patients who have subsequently conceived, whether attending a fertility clinic or not. One woman (para 1) has not succeeded in conceiving. Her pregnancy was terminated by extra-amniotic prostaglandins at 14 week's gestation because of fetal anencephaly. There were no complications at the time of termination, surgical evacuation was not performed, and antibiotics were not given. An uneventful recovery was noted at 6 weeks, but when contacted 2 years after termination the woman reported difficulty with conceiving. She had not sought help from her doctor or a fertility clinic and a further communication with her general practitioner indicated that the woman and her husband had since divorced. Thirty-six women have not tried to become pregnant since termination. None reported that they had wished to become pregnant at the time of our inquiry. Eight women or their husbands had been sterilized.

Comment Follow-up after therapeutic abortion of the woman seeking information about potential consequent morbidity requires considerable care and caution. Inquiry without prior warning into subsequent fertility and pregnancy performance could cause inappropriate anxiety. We therefore reasoned that women whose pregnancies had been terminated for suspected fetal disease would represent a group most likely to attempt a further conception during the first 1 to 2 years after termination, and that such women would be more cooperative with long-term follow-up studies. Our results have supported this view, as 97% of those conceiving embarked on another pregnancy within 2 years. Satisfactory interpretation of results of postabortion follow-up studies requires that the observations be controlled. We believe that the ideal control item for future fertility of a patient is that patient's previous fertility history. Other control subjects may introduce unacceptable bias-nulliparous women are inappropriate

Fertility after second-trimester induced abortion

1139

because their fertility has not been proved 7 and studying the women who enter an antenatal clinic overlooks all those currently unsuccessful in conceiving." Our present results suggest that the initial prostaglandin-induced abortion had an insignificant effect on future fertility. Only one woman in 140 had not achieved an apparently desired pregnancy since the indexed termination; there remains some doubt, however, about her failure to conceive because no fertility investigations were performed. Furthermore, the woman and her husband have since divorced, and the part this played in her failure to conceive remains uncertain. These results are thus at considerable variance with the calculated infertility rates quoted by others. Louros 9 reported that 30% of women remained irreversibly infertile after pregnancy termination, while Trichopoulus et al., 10 observing women attending an infertility clinic, concluded there was a 3.4-fold increased risk of infertility in women with a previously terminated pregnancy as compared with those with no history of previous spontaneous or induced abortion. Both these studies have involved abortion in a country in which pregnancy termination was not legal, and the findings could be explained by the report of Joupilla et al.," who reported tubal pathologic findings in 18% of93 women examined by hysterosalpingography after pregnancy termination. In that study, however, termination method and gestational age at abortion were not recorded. More recent reports have suggested less pessimistic outcomes, but generally have overlooked the possibility of "total" infertility. Obel8 collected data at an antenatal clinic and found that the time to conceive after discontinuing contraceptive methods was similar in women whose previous pregnancy had been legally terminated and in those previously delivered of a living child; those failing to conceive in the two groups, however, would not have been considered. Daling et a!." failed to find any association between previous induced abortion and sub fertility in women attending an infertility clinic compared with those attending for antenatal care. However, their study was retrospective and gives no guide to the population at risk. Stubblefield et al. 12 approached the issue by following patients prospectively after an induced abortion, a term delivery, or a gynecologic clinic appointment. In the latter two groups 20% and 28%, respectively, gave a history of previous therapeutic abortion. These authors found no difference in cumulative pregnancy rates in the three groups; however, patients were only included in the study for as long as they returned questionnaires (up to 30 months). Their subsequent pregnancy rate was 189 of 1234 patients (15.3%), and the drop-out rate for followup reached 50% by 9 months. Dalaker et al. 13 succeeded in getting completed questionnaires returned in 73.5%

1140 MacKenzie and Fry

of 690 women whose pregnancy had been terminated by unspecified methods 4 to 7 years previously and a similar number of women delivered at term over the same period. Thirty-one percent of the postabortion group had subsequently conceived, while the sterility rate was reported at 3.6% compared with 2.1% for the control group, a statistically insignificant difference. Abortion management and further follow-up details are not available. We have succeeded in obtaining data on all our patients and our analysis does not overlook genuine infertility unless the individual patient elected to deny its existence. Unlike most other reports concerned with postabortion morbidity in which the abortion method and gestation have been varied or unspecified, we have concentrated on second-trimester abortion induced with prostaglandins. Particularly relevant is the fact that prophylactic antibiotics were not used at the time of initial termination; Obel8 observed higher infertility rates in patients in whom sepsis was suspected at the time of abortion. We have previously argued 14 that prophylactic antibiotics are not justified for routine pregnancy termination, and the present results would appear to vindicate that view. While we acknowledge that our results may apply only to outcomes after midtrimester abortion induced with prostaglandins, we have no reason to believe that other methods of termination should lead to a significantly different outcome. We therefore conclude that if appropriate care is taken at the time of pregnancy termination, there is little risk of subsequent infertility. We thank the patients and general practitioners for their cooperation in this study and Dr. Adrian Grant, National Perinatal Epidemiology Unit, Oxford, for advice on the preparation of the manuscript.

May 1988 Am J Obstet Gynecol

REFERENCES I. Daling JR, Emanuel I. Induced abortion and subsequent outcome of pregnancy. Lancet 1975;2: 170-2. 2. MacKenzie IZ, Hillier K. Prostaglandin induced abortion and outcome of subsequent pregnancies: a prospective controlled study. Br MedJ 1977;2:114-7. 3. van der Slikke JW, Treffers E. Influence of induced abortion on gestational duration in subsequent pregnancies. Br Med J 1978; 1:270-2. 4. MacKenzie IZ, Hillier K. Delayed morbidity following prostaglandin induced abortion. Int J Gynecol Obstet 1975; 13:209-14. 5. MacKenzie IZ, Embrey MP. Single extra-amniotic injection of prostaglandins in viscous gel to induce abortion. Br J Obstet Gynaecol 1976;83:505-7. 6. MacKenzie IZ, Sayers L, Bonnar J, Hillier K. Coagulation changes during mid trimester abortion induced with intraamniotic prostaglandin E2 and hypertonic solutions. Lancet 1975;2: 1066-9. 7. Daling J, Spadoni LR, Emanuel I. Role of induced abortion in secondary infertility. Obstet Gynecol 1981;57:5961. 8. Obel EB. Fertility following legally induced abortion. Acta Obstet Gynecol Scand 1979;58:539-42. 9. Louros NC. Proc Acad Athens 1967;42:396, quoted by Pantelakis SN, Papadimitrious GC, Doxiadis SA. Influence of induced and spontaneous abortions on the outcome of subsequent pregnancies. AM J 0BSTET GYNECOL 1973; 116:799-805. 10. Tricholpoulos D, Handanos N, Danezis J, Kalandidi A, Kalapothaki V. Induced abortion and secondary infertility. Br J Obstet Gynecol 1976;83:645-50. 11. Jouppila P, Kauppila A, Pun to L. Observations on patients 2 years after legal abortion. IntJ Fertill974;19:233. 12. Stubblefield PG, Manson RR, Schoenbaum SC, Wolfson CE, Cookson DJ, Ryan KJ. Fertility after induced abortion: a prospective follow-up study. Obstet Gynecol 1984;62:186-93. 13. Dalaker K, Lichtenberg SM, Okland G. Delayed reproductive complications after induced abortion. Acta Obstet Gynecol Scand 1979;58:491-4. 14. MacKenzie IZ, Fry A. Post-abortal sepsis and prophylactic antibiotics. Br MedJ 1981;282:476-7.