1 University College London Hospitals NHS Trust, The Reproductive Medicine Unit and 2 Department of Endocrinology, The Middlesex Hospital, Mortimer Street, London W1N 8AA, UK
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Abstract |
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Key words: maternal hypopituitarism/ovulation induction/pregnancy outcome
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Introduction |
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We have audited the outcome of all pregnancies in women with panhypopituitarism attending the fertility clinics of University College London Hospitals between 1980 and 2000 with the purpose of determining whether spontaneous labour and lactation was possible in the absence of pituitary function and to document fetal outcome.
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Materials and methods |
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Results |
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Ten of the 11 live-born babies were delivered by Caesarean section and in one the mode of delivery was unknown. There were six emergency Caesarean sections; two for fetal distress, two for pre-term rupture of membranes and malpresentation, one for failure to progress and one failed induction of labour. There were four elective Caesarean sections, one for suspected intrauterine growth restriction, one for a high head at term and two repeat. All women received i.v. hydrocortisone replacement 50100 mg three times daily for three doses during delivery. There was one case of puerperal psychosis.
One of the nine women did not have a live birth and we have no data for one woman. Of the remaining seven women, only one woman successfully breast-fed while another abandoned breast-feeding after one week. Five women bottle-fed their babies; three had `no milk', one had two pregnancies, both babies were born prematurely with `poor sucking' and one elected to bottle-feed. The three women with no milk production had prolactin levels of 124, 53 and <50 mIU/l (normal range 0660).
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Discussion |
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Regimens of ovulation induction in hypopituitarism are worthy of comment. Where a structural lesion of the pituitary is the underlying pathology the GnRH pump is unlikely to be effective (Morris et al., 1987). In any instance of gonadotrophin deficiency treatment regimens should include preparations with LH activity in order to ensure an adequate estrogen response (Shoham et al., 1991
). Further, there is anecdotal evidence that GH replacement might be beneficial in hypopituitarism when the response to conventional gonadotrophin therapy is poor (Salle et al., 2000
).
The previous literature describing pregnancy outcome in panhypopituitarism consists of seven papers reporting on nine women (Polishuk et al., 1965; Corral et al., 1972
; Bowers and Jubiz, 1972; Gemzell, 1973
; Jorgensen et al., 1973
; Grimes and Brooks, 1980
; Golan et al., 1990
). There were nine live births comprising seven singletons and two sets of twins. Five of the nine women were delivered by Caesarean section and four had vaginal deliveries. Seven women were unable to breast-feed, with no milk, and there was no comment on feeding for two of the women. Details of gestational age and birth weights were scant. Our single centre series of nine women may be more representative of pregnancy outcome in panhypopituitary women compared with case reports. Women ascertained on the basis of deficiency of GH alone have been reported to have had a much more favourable outcome than that reported here for panhypopituitarism, with a Caesarian section rate of 50% (de Boer et al., 1997
) and low birth weight of 25% (Curran et al., 1998
). Pituitary GH deficiency, however, is unlikely to be the main contributor to poor pregnancy outcome in this group because placental GH can compensate for its action (Verhaeghe et al., 2000
).
The poor outcome for twin pregnancies reported here highlights the importance of ensuring unifollicular ovulation in this group of women, with careful ultrasonographic monitoring. More conservative criteria for the number of mature follicles allowed to develop may be required in this subgroup of infertile women compared with others.
Half of the live births were small for gestational age with birth weights on or below the 10th centile, which could be a reflection on maternal short stature as smaller, lighter mothers have lighter babies. This again raises the issue of intrauterine GH deficiency, as a role for pituitary GH in the regulation of fetal body weight during late gestation has been demonstrated in rats (Nogami et al., 1995). Indeed, one case report advocates the use of GH replacement during pregnancy in GH deficient women despite the action of placental GH (Muller et al., 1995
).
The incidence of Caesarean section in our series is striking. It may be that these `precious pregnancies' trigger early obstetric intervention. Interestingly, in the two cases of fetal demise, delivery was vaginal indicating that labour and vaginal delivery are possible where fetal condition is not a consideration. Of the seven women, only one woman successfully breast-fed, presumably because of prolactin deficiency. However, successful breast-feeding has been reported despite undetectable prolactin concentrations postpartum (Franks et al., 1977).
We conclude that the obstetric outcome of these pregnancies suggests that they should be treated as high risk. It may be that greater attention to preparation of the uterus prior to conception, perhaps with the addition of GH, will improve the outcomes reported here. Twin pregnancy carries a particularly poor outcome and should be avoided at all costs with more conservative criteria for the triggering of ovulation than might be applied to women with normal pituitary function. Fetal growth should be followed by serial ultrasound to detect intrauterine growth restriction and delivery by elective Caesarean section discussed.
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Acknowledgements |
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Notes |
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References |
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Submitted on December 12, 2001; accepted on February 8, 2002.