1 Hull Maternity Hospital and Departments of 2 Obstetrics and Gynaecology and 3 Medicine, University of Hull, Hull, UK
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Abstract |
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Key words: donor insemination/hypertension of pregnancy/IVF/pre-eclampsia
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Introduction |
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An inverse relationship has been suggested between the duration of sexual co-habitation and the incidence of pregnancy-induced hypertension (PIH) (Robillard et al., 1994), with rates of PIH in excess of 30% for under 4 months sexual co-habitation and rates of below 10% for over 12 months. Barrier contraception has also been linked to an increased rate of pre-eclampsia (Klonoff-Cohen et al., 1989
). These observations have led to the development of various theories of immunological responses in the mother against the antigens in the partner's semen, which would seem to protect against the development of hypertensive disease of pregnancy.
This study aims to compare the incidence of hypertensive disease of pregnancy in women who conceived by assisted fertility techniques with their partner's spermatozoa to those who conceived with donor spermatozoa, to which they were completely immunologically naive. By selecting the population of women attending the local IVF clinic, most of the women presenting for treatment for subfertility would have been exposed to their partner's semen for a duration in excess of 3 years. They would also mostly be nulliparous and thus at greater risk of gestational hypertensive disease. The hypothesis was that those women conceiving by IVF with their partner's spermatozoa would have been exposed to its antigens for some time and should experience a protective effect, whilst those conceiving by donor spermatozoa would be immunologically naive to it and should experience increased rates of hypertensive disease.
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Materials and methods |
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Data were collected from the IVF unit on all the pregnancies achieved between 1991 and 1998 who booked for maternity care in one of the two local maternity units. Pregnancies from out of the region were excluded. The duration with partner (where documented), the method of conception and the origin of paternity (including previous number of attempts with each donor) were recorded and anonymized by the researcher (W.L.N.). The maternity notes were then traced at the two local maternity hospitals (Hull Maternity Hospital, Hull and Castle Hill Hospital, Cottingham, UK). When data were collected from the maternity notes, the researcher (G.H.H.) was blinded to the method of conception and origin of paternity. Details of obstetric outcome, antenatal, intrapartum and postnatal blood pressure readings, proteinuria and other complications were all recorded.
The classification of hypertensive diseases of pregnancy first proposed by Davey and MacGillivray (Davey and MacGillivray, 1988) was used. These criteria were applied strictly to classify the hypertensive diseases. The definition of proteinuria required either 300 mg per 24 h in a 24 h urine specimen or two mid-stream specimens more than 4 h apart with 2+ proteinuria on dipstick testing or 1+ by dipstick testing with measured specific gravity <1.03 and pH <8. Women were only classified as having proteinuria when full documentation allowed classification as described.
All results were analysed using Statistics Package for Social Sciences (SPSS Professional Statistics, SPSS Inc., Illinois, USA) and the 2 test was used to show the level of significance of the rates of hypertensive disease in partner and donor sperm groups.
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Results |
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There were no differences in the demographics between the partner and donor groups as outlined in Table I. Apart from one spontaneous conception the other 227 pregnancies were conceived using techniques that involved washed spermatozoa.
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The frequency of hypertensive disorders is outlined in Table II, and it is clear that there were no differences between partner and donor sperm groups. A subgroup analysis confined to nulliparous women excluded any effects of multiparity and again demonstrated no differences.
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Multiple logistic regression analysis was performed, addressing all recorded variables which may have relevance, including: age, booking weight, booking height, booking systolic blood pressure, booking diastolic blood pressure, number of fetuses, sex of fetuses, parity, smoking, origin of paternity, early pregnancy loss rate, aspirin use, triple test result, use of antihypertensives and incidence of bleeding in pregnancy. The only variables which predicted a risk of hypertensive disease of pregnancy in the model were multiple pregnancy (P < 0.005) and raised booking systolic blood pressure (P < 0.0005).
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Discussion |
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In 1977 it was reported (Marti and Herrmann, 1977) that there was an increased incidence of mild to moderate hypertensive disease in a small group of primigravid women who had less preconceptional exposure to spermatozoa than did their control group. They postulated that sperm histocompatibility antigens induced an immunological tolerance that prevented an immune reaction. Some controversy exists over the expression of human leukocyte antigens (HLA) on spermatozoa, although it seems that HLA antigens are present in the seminal plasma fraction of the ejaculate (Singal and Berry, 1972
) and that these may be adsorbed onto the surface of the sperm plasma membrane.
Since then much research has focused on the immunological theories. Findings have been discrepant in all areas of this subject and controversy prevails. The use of barrier contraception prevents maternal exposure to semen and may be associated with an increased risk of hypertensive disease. This is suggested by a case controlled study of 115 women with pre-eclampsia, which showed a 2.37-fold increased risk of pre-eclampsia among users of barrier contraception (Klonoff-Cohen et al., 1989). However combined data on 13 914 pregnancies from two prospective studies of pre-eclampsia rates showed no association between pre-eclampsia rates and barrier contraception (Mills et al., 1991
).
An inverse relationship between the self-reported duration of sexual co-habitation before conception and the incidence of PIH has been reported in a population of Caribbean women (Robillard et al., 1994). In this study the incidence of PIH in pregnancies where the duration of co-habitation was under 4 months was 32%, and the incidence when the duration of co-habitation was over 12 months was 3%. This would seem to support the theory that immunological exposure to semen protects against PIH.
The issue of hypertensive disease in pregnancies from donor insemination has been addressed previously. The outcome of 584 pregnancies resulting from artificial insemination by donor was analysed retrospectively by an Australian group, who described an overall incidence of pre-eclampsia of 9.3% and claimed this was substantially increased over the expected (Need et al., 1983), although they went on to describe a background pre-eclampsia rate of 7.3% in their institution. A Canadian group looked at a total cohort of 81 patients, 44 with partner insemination and 37 with donor (Smith et al., 1997
). They reported three cases of pre-eclampsia in the partner group and nine in the donor. A series of 44 pregnancies following donor insemination has been reported (Perkins, 1993
) and no difference was found in hypertensive complications from expected rates in their institution.
A group from Finland (Laivuori et al., 1998) has studied a cohort of 123 pregnancies and found no increased rate of hypertensive disease with donor spermatozoa. However their report was confined to antenatal gestational proteinuric hypertension, which excluded a significant proportion of hypertensive disease of pregnancy. The current research adds to the data from these previous studies by including a larger cohort of patients than some and by methodologically addressing the question from another angle. Like with like was compared by using subfertility patients as controls, to exclude any confounding influence of subfertility on rates of hypertensive disease.
The immunological theories of hypertensive disease are also supported by the finding that oocyte donation may be associated with increased rates of the disease. A rate of 25.7% gestational hypertension in 35 recipients of oocyte donation versus 4.2% in a control group of 95 IVF patients has been reported in one series (Hendler et al., 1997). A group in the UK has studied a cohort of 33 women conceiving with donor spermatozoa, 27 with donor eggs and 12 women with embryo donation, and compared them with a control group of matched patients conceiving spontaneously (Salha et al., 1999
). They found the incidence of both PIH and pre-eclampsia to be increased in the group with donated gametes (12.5% and 18.1% respectively), but the background rates of PIH of 2.8% and pre-eclampsia of 1.4% were much lower than that found in other studies. Another study of 1552 donor insemination pregnancies has reported an odds ratio of 1.4 for the development of pre-eclampsia when compared to normally conceived pregnancies, although the details of the classification of the data are not given clearly (Hoy et al., 1999
).
The total of 218 completed pregnancies for which full maternity data could be examined and analysed gives the present study a cohort of patients greater than required by power calculations. The sample size needed was calculated to show a 20% reduction (from 30 to 10%) in the incidence of hypertensive disease as found in a cohort of Caribbean women (Robillard et al., 1994). In South Africa it was estimated that by using the same strict definitions of hypertensive disease the expected rate was 30% (Davey and MacGillivray, 1988
). In the current study the total overall rate of hypertensive disease was 24%. A much larger sample size would be needed to exclude differences of a smaller magnitude in rates of hypertensive disease between donor and partner groups. The age distribution of patients, gestation at delivery, high percentage of nulliparous women and occurrence of multiple pregnancy was as would be expected for a cohort of women attending a fertility service. The mode of delivery was also in keeping with expectations, as the threshold to deliver by Caesarean section is recognized to be lower in women conceiving by assisted reproduction (Söderström-Anttila et al., 1998
).
Hypertensive disease was observed in 23.9% of pregnancies in the current study, which is within keeping with that found in a cohort of South African women, with 40% of these cases being non-proteinuric antenatal gestational hypertension (Davey and MacGillivray, 1988). The distribution of cases through all categories of the classification of hypertensive disorders, from mild to severe, was uniform between donor and partner groups. Thus, within the confines of the power calculation, if any difference between donor and partner insemination existed it would have been detected.
This study does not show that partner insemination is associated with reduced rates of hypertensive disease of pregnancy. If pre-eclampsia has an immunological basis it is not reduced by previous exposure to the fertilizing spermatozoa. This study therefore challenges the evolving theory of sexual co-habitation.
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Acknowledgments |
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Notes |
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References |
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Submitted on May 15, 2000; accepted on October 23, 2000.