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High-Risk Pregnancy Management in Women with Hypopituitarism

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High-Risk Pregnancy Management in Women with Hypopituitarism Journal of Perinatology (2009) 29,89–95 r 2009 Nature Publishing Group All rights reserved. 0743-8346/09 $32 www.nature.com/jp COMMENTARY High-risk pregnancy management in women with hypopituitarism KKu¨bler1,2, D Klingmu¨ller2, U Gembruch1 and WM Merz1 1Department of Obstetrics and Gynecology, University of Bonn, Bonn, Germany and 2Institute for Clinical Chemistry and Pharmacology, University of Bonn, Bonn, Germany obstetric complications.1 To assess specific risks during gestation Pregnancy after complete loss of pituitary function is uncommon. However, and parturition of women lacking pituitary hormones, we advances in fertility treatment have led to increased pregnancy rates in performed a literature review revealing adverse pregnancy outcome. hypopituitary women. We hereby present a literature review of pregnancies Furthermore, we compared affected cases with published controls affected by hypopituitarism, including a comparison with published and identified significantly higher rates of cesarean delivery, controls; further, we add one case report of severe hypopituitarism where transverse lie and small for gestational age (SGA) neonates, third-trimester oxytocin supplementation was performed. As only limited indicating the need for close maternal and fetal surveillance. information is available on management and outcome, our purpose was to We assumed that the adverse pregnancy outcome might reflect determine obstetric complications associated with deficiency of pituitary uterine dysfunction caused by hormone deficiency, including lack hormones. The analysis of 31 pregnancies in 27 women revealed that of oxytocin. Oxytocin is a potent uterotonic agent, synthesized in hypopituitary women are at increased risk: postpartum hemorrhage the hypothalamic nuclei, transported to the posterior pituitary and occurred in 8.7%, transverse lie in 16%; 42.4% of the newborns were small released into the general circulation in a pulsatile manner.2 for gestational age. These findings are supposedly the result of uterine Oxytocinergic pathways may be adversely affected in hypopituitary dysfunction caused by hormone deficiency. Oxytocin supplementation was women, resulting in alterations of delivery and lactation. To performed with the aim to establish physiologic conditions and to prevent compensate for oxytocin deficiency, we performed supplementation postpartum uterine inertia. In this case substitution may have contributed between the gestational age (GA) of 34 þ 0 weeks and delivery in a to correct fetal presentation but did not prevent postpartum hemorrhage. patient lacking pituitary hormones. The rationale for this Further investigations into both oxytocin-dependent and -independent experimental treatment was to enhance uterine function. We mechanisms regulating uterine contractions and contractility are necessary hypothesized that oxytocin substitution may augment uterine to develop strategies for prevention of uterine inertia in oxytocin-deficient contractility, thereby preventing fetal malpresentation and pregnancies. postpartum hemorrhage (PPH). This is the first report of third- Journal of Perinatology (2009) 29, 89–95; doi:10.1038/jp.2008.116 trimester oxytocin substitution in hypopituitarism because a search Keywords: oxytocin; hypopituitarism; high-risk pregnancy; malpresen- of Medline (English language; search terms: oxytocin, tation; postpartum hemorrhage supplementation, substitution, pregnancy) revealed no other cases. Introduction Normal functions of the hypothalamic–pituitary-target axes are Methods important for the regulation of feto-maternal homeostasis. A search was performed using Medline (October 1965 to April 2006) Consequently, deficiency of pituitary hormones may affect with the following MeSH or keyword terms (single and in conception, pregnancy and delivery. Although advances in artificial combination): hypopituitarism, oxytocin, pregnancy, delivery and reproductive techniques (ARTs) provide methods to restore fertility outcome. Titles and abstracts published in English were searched in hypopituitary women, only few cases of successful pregnancy for relevant information and hard copies retrieved for further and parturition have been published, reporting high rates of information. References were analyzed by hand to identify additional publications. From all identified articles, two Correspondence: Dr WM Merz, Department of Obstetrics and Gynecology, University of Bonn, investigators selected the reports to be reviewed and extracted data Sigmund Freud Strasse 25, Bonn 53127, Germany. E-mail: [email protected] from these. As pregnancy in hypopituitarism is rare, we accepted Received 14 March 2008; revised 25 June 2008; accepted 5 July 2008 case reports as well as retrospective trials. Unpublished data or Pregnancy management in hypopituitarism KKu¨bler et al 90 published abstracts were not included. We did not attempt to group of hypopituitary pregnancies (n ¼ 16) and the ART control contact authors. group (n ¼ 16),35, respectively. A total of 28 documents comprising 63 pregnancies in 40 As only few cases were observed in the study group, the women were identified.1,3–29 Inclusion criteria for the study statistical analysis was obtained by simulation procedure with the group were as follows: pregnancies conceived by ART, resulting statistical software ‘R’ (version 2.1.0, The R Foundation for in viable babies. We further evaluated causes of hypopituitarism Statistical Computing, Vienna, Austria). Distributions were and considered only cases where posterior pituitary damage compared using the Fisher’s exact test. The level of statistical was likely.30,31 The following cases were excluded: significance was set at P<0.05. subclinical hypopituitarism (n ¼ 16);4,6,8,11–13,17,19,25,28,29 cause of hypopituitarism not specified (n ¼ 1);21 first-trimester miscarriages (n ¼ 15).1,4,12,19 Sixteen case Case reports3,5–7,9,10,14–16,18,20,22–24,26,27 describing the outcome of A 35-year-old woman had undergone subtotal excision of a 18 pregnancies and one trial1 reporting 13 pregnancies in nine craniopharyngioma at the age of 8 years. The resulting pituitary women were included in the analysis. The following data were insufficiency was treated with substitution of L-thyroxine, analyzed: baseline characteristics (age at diagnosis and pregnancy, hydrocortisone, desmopressin and growth hormone. At 12 years of cause and therapy of hypopituitarism, ovulation induction, age, recurrence was diagnosed and reoperation performed. obstetric history); course of pregnancy (pregnancy-specific Subsequently, she underwent radiation therapy for residual tumor. complications, drug substitution); delivery (mode of delivery Post-interventional panhypopituitarism was diagnosed and (MOD), GA); puerperium (onset of lactation, maternal complete substitution of pituitary hormones initiated. The patient complications) and fetal outcome (birth weight, perinatal remained disease-free thereafter. At the age of 19, menstrual cycle morbidity and mortality). Weight centiles corrected for GA and was established by combined oral contraceptives. The patient singleton versus multiple pregnancy were calculated according to requested fertility treatment at the age of 30 years and ovulation ethnicity and sex.32–34 In case the sex was not reported, the centile induction with gonadotropins was performed. The third cycle of was adjusted as a minimum for both sexes. in vitro fertilization (IVF) with intracytoplasmic sperm injection To determine specific pregnancy-related risks in hypopituitary (ICSI) resulted in a singleton intrauterine pregnancy. Progesterone women, the study group was compared to published controls.35–37 was substituted until 12 weeks’ GA. Assessment of adequate The analysis was limited to singleton pregnancies because substitution of pituitary hormones involved both clinical and complication rates are higher for multiple pregnancies. Owing to biochemical evaluations. Hydrocortisone dosage had to be the fact that comparisons may be hampered by maternal increased from 5 mg daily preconceptionally to 10 mg per day (17 differences between the groups we tried to adjust as many weeks’ GA), 15 mg per day (24 weeks’ GA) and 25 mg per day (32 confounding factors as possible. Matching criteria for published weeks’ GA) for the remaining pregnancy. L-Thyroxine (125 mg per epidemiological studies were as follows: singleton pregnancies day) and desmopressin (0.4 mg per day) did not require received after ART, mean maternal age, proportion of primiparity adjustment. The patient was referred to our department for p20% and mean GAp1 week difference, date of parturition antenatal care at 16 þ 4 weeks’ GA and was seen monthly until between 1965 and 2005, delivery in developed countries and 34 þ 0 weeks’ GA. No maternal complications occurred and fetal definition of adverse outcome. The following pregnancy development was normal. complications were analyzed: SGA (birth weight p10th centile), As oxytocin-deficiency was presumed, we performed third- transverse lie at term (confirmed by cesarean section), PPH (blood trimester substitution. After obtaining informed consent loss requiring blood transfusion and/or blood loss resulting in incremental doses of intravenous (i.v.) oxytocin under hysterectomy and/or medical treatment to induce uterine cardiotocographic monitoring were administered at 34 þ 0 weeks’ contractions), cesarean delivery (in case of one woman with more GA to define the amount of oxytocin required to induce uterine than one pregnancy, the repeat cesarean section
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