Department of Obstetrics and Gynaecology, The University of Wuerzburg, Josef-Schneider-Str. 4, D-97080 Wuerzburg, Germany
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Abstract |
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Key words: endocrine factors/hyperprolactinaemia/obesity/recurrent spontaneous abortion
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Introduction |
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Little information is available on the role of endocrine abnormalities during the follicular phase as possible risk factors for recurrent spontaneous abortion. Both phases of the menstrual cycle have to be considered together, as luteal defects are frequently associated with inadequate follicular growth, premature luteinization or basal hormone imbalances during the follicular phase (Soules et al., 1989).
Therefore, we investigated the frequency of abnormalities of basal hormone concentrations in women with recurrent spontaneous abortion in whom no other underlying cause for the repeated loss was apparent. We aimed to identify endocrine risk factors during follicular phase associated with recurrent spontaneous abortion.
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Materials and methods |
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Control subjects (n = 42) were nulligravid women of similar age (mean ± SD: 33.3 ± 4.7 years, range 2441) with no previously recognized miscarriage, and no clinical evidence of endocrine abnormality. They were attending our assisted reproduction clinic for tubal or male factor infertility. Twenty-four women had regular ovulatory cycles and four suffered from oligomenorrhoea. In one of these patients, polycystic ovaries could be demonstrated by vaginal ultrasound.
None of the patients or controls was pregnant at the time of the study or in the 6 months beforehand, and none was taking any medication likely to affect results (e.g. oestrogens, progestagens, dopamine antagonists and glucocorticoids).
The body mass index (BMI) of each study and control subject was calculated using the formula weight (kg)/height (m2) (study group mean ± SD: 26.1 ± 6.4 kg/m2, range 19.935.6 kg/m2; control group mean ± SD: 22.6 ± 3.0 kg/m2, range 17.133.4 kg/m2). Women with a BMI 25 kg/m2 were regarded as obese.
All subjects gave informed consent.
Endocrine evaluations
Fasting blood samples were taken routinely between 8.00 and 10.00 a.m. after a resting period of 30 min during the early follicular phase. Hormonal analyses were performed using commercially available radioimmunoassays for follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, (Serono, Freiburg, Germany), testosterone, androstenedione, dehydroepiandrostenedione, oestradiol, progesterone and 17-OH-progesterone (Biermann, Bad Nauheim, Germany). Thyroid stimulating hormone (TSH) was measured using an automated fluorimetric enzyme immunoassay (Chemilumineszenz IXM; Abbott, Wiesbaden, Germany). The normal ranges were taken from the manufacturer's instructions. They are given in Table I. Both the variability within and that between assays were <10%.
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Results |
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Table II shows the frequency of abnormal endocrine test results in both groups. Abnormal FSH and LH concentrations were equally distributed in the study and control groups. The prevalences of hyperprolactinaemia and of raised androstenedione concentrations were higher in study women than in controls. Thirteen patients had elevated prolactin concentrations, another four patients had elevated androstenedione concentrations, whereas in two women in the study group, both prolactin and androstenedione concentrations were raised. Twenty-three study women and five control women were obese (P = 0.0001). In Table III
, the amount of abnormal endocrine test results in obese compared to non-obese women, whether they belong to the study or the control group, is shown.
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Discussion |
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Our finding of increased serum concentrations of androstenedione is supported by the observation of an increased miscarriage rate in women with polycystic ovarian disease, a disorder which is characterized by amenorrhoea, hirsutism, and raised androgen concentrations. The prevalence of polycystic ovarian disease in women with recurrent spontaneous abortion has been reported to be between 44% (Tulppala et al., 1993) and 82% (Clifford et al., 1994
). A similar frequency of polycystic ovaries was also observed in this study. It is surprising that we were unable to detect raised concentrations of serum testosterone in women with recurrent spontaneous abortion, as testosterone is the androgen with the highest sensitivity for the disorder (Goldzieher, 1981
) and as high serum concentrations of testosterone, free testosterone and dehydroepiandrostenedione were associated with an increased miscarriage rate in one study (Tulppala et al., 1993
). We did not observe increased concentrations of dehydroepiandrostenedione in our study. These divergent observations may be partly explained by the known variability of the clinical and endocrine features associated with polycystic ovarian disease.
Several studies have been reported that hypersecretion of basal LH with or without polycystic ovaries is a risk factor for miscarriage (Turner, 1991; Watson et al., 1993
; Chandler, 1994
; Clifford et al., 1994
). It has been stated that high basal LH concentrations, leading to premature luteinization, may be found in up to 33% of women with recurrent spontaneous abortion (Clifford et al., 1994
). In contrast, we observed a high basal LH in only one woman in the study group, which argues against its use as a diagnostic test for endocrine-mediated abortion.
Hyperprolactinaemia and hypoprolactinaemia have been causally related with luteal phase defects and with miscarriage (Gu, 1993; Ando et al., 1994
), a finding which is supported by our observation of a significant excess of hyperprolactinaemia in women with recurrent spontaneous abortion. Medical suppression by dopamine antagonists proved effective in preventing miscarriage in one study (Ando et al., 1994
). We are unable to comment on the effectiveness of prolactin antagonists in preventing pregnancy loss in our study.
Our observation of normal serum TSH concentrations in all but one study group women is supported by previous investigators who reported a relatively low prevalence of abnormal thyroid function (~2%) in women with recurrent spontaneous abortion (Harger et al., 1983; Stray-Pederson and Stray-Pederson, 1984
). Despite this low frequency, we still think that TSH screening is generally warranted in all women with recurrent spontaneous abortion because both hypothyroidism and hyperthyroidism are easy to correct medically.
In conclusion, we observed an increased rate of prolactin and androgen abnormalities in women with recurrent spontaneous abortion. It is possible that these disturbances may be causally related to miscarriage. Identification of these women with presumably `endocrine-mediated' abortions may make them amenable to endocrine therapeutic strategies for the prevention of further miscarriage.
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Notes |
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References |
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Ardaens, Y., Robert, Y., Lemaitre, L. et al. (1991) Polycystic ovarian disease: contribution of vaginal endosonography and reassessment of the ultrasonic findings. Fertil. Steril., 55, 10621068.[ISI][Medline]
Balen, A.H., Tan, S.L. and Jacobs, H.S. (1993) Hypersecretion of luteinizing hormone: a significant cause of infertility and miscarriage. Br. J. Obstet. Gynecol., 100, 10821089.[ISI][Medline]
Bulletti, C., Flamigni, C. and Giacomucci, E. (1996) Reproductive failure due to spontaneous abortion and recurrent miscarriage. Hum. Reprod. Update, 2, 118136.
Chandler, C.J. (1994) Hypersecretion of luteinizing hormone: a significant cause of infertility and miscarriage. Br. J. Obstet. Gynecol., 101, 737738.
Clifford, K., Rai, R., Watson H. et al. (1994) An informative protocol for the investigation of recurrent miscarriage: preliminary experience of 500 consecutive cases. Hum. Reprod., 9, 13281332.[Abstract]
Coulam, C.B. and Stern, J.J. (1994) Endocrine factors associated with spontaneous abortion. Clin. Obstet. Gynecol., 37, 730744.[ISI][Medline]
Franks, S. and Hamilton-Fairley, D. (1994) The role of body weight and metabolic abnormalities in ovulation induction. Contracept. Fertil. Sex., 22, 178179.[ISI][Medline]
Ginsburg, K.A. (1992) Luteal phase defect etiology, diagnosis and management. Endocrinol. Metab. Clin. North Am., 21, 85104.[ISI][Medline]
Goldzieher, J.W. (1981) Polycystic ovaries disease. Fertil. Steril., 35, 371376.[ISI][Medline]
Gu, F. (1993) Effect of serum prolactin levels on luteal function in patients with recurrent abortions. Chung Hua Fu Chan Ko Tsa Chih, 28, 3437.[Medline]
Harger J.H., Arcger, D.F., Marchses, S.D. et al. (1983) Etiology of recurrent pregnancy losses and outcome of subsequent pregnancies. Obstet. Gynecol., 62, 574581.[Abstract]
Lim, K.J., Odukoya, O.A., Li, C. et al. (1996) Cytokines and immuno-endocrine factors in recurrent miscarriage. Hum. Reprod. Update, 2, 469481.
McNeely, M.J. and Soules, M.R. (1989) The diagnosis of luteal phase insufficiency: a critical review. Fertil. Steril., 51, 582587.[ISI][Medline]
Quensby, S.M. and Farquharson, R.G. (1993) Predicting recurrent miscarriage: what is important? Obstet. Gynecol., 82, 132138.[Abstract]
Searle, E., Aplin, J.D., Li, T.C. et al. (1994) Endometrial differentiation in the peri-implantation phase of women with recurrent miscarriage: a morphological and immunohistochemical study. Fertil. Steril., 62, 989996.[ISI][Medline]
Soules, M.R., McLachlan, R.I., Ek, M. et al. (1989) Luteal phase deficiency characterization of reproductive hormones over the menstrual cycle. J. Clin. Endocrinol. Metab., 69, 804812.[Abstract]
Stray-Pederson, B. and Stray-Pederson, S. (1984) Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of habitual abortion. Am. J. Obstet. Gynecol., 148, 140146.[ISI][Medline]
Tulppala, M., Stenman, U.H., Cacciatore, B. et al. (1993) Polycystic ovaries and levels of gonadotropins and androgens in recurrent miscarriage: prospective study in 50 women. Br. J. Obstet. Gynecol., 100, 348352.[ISI][Medline]
Turner, M.J. (1991) Raised luteinizing hormone and miscarriage. Lancet, i, 742.
Watson, H., Kiddy, D.S., Hamilton-Fairley, D. et al. (1993) Hypersecretion of luteinizing hormone and ovarian steroids in women with recurrent early miscarriage. Hum. Reprod., 8, 829833.[Abstract]
Submitted on January 12, 1998; accepted on September 29, 1998.