This prospective cohort study of infertility patients compared testosterone concentrations in early pregnancy in infertility patients who conceived naturally or after treatment. Although all groups demonstrated some increase in pregnancy testosterone from baseline concentrations, subjects who conceived following ovulation induction showed a significantly increased rise in testosterone as compared with controls (P < 0.01).
Introduction
Ovarian stimulation is the cornerstone of infertility treatments in conjunction with either intrauterine insemination (IUI) or IVF. Medications that stimulate the ovaries to produce multiple oocytes also create multiple corpora lutea, which may lead to supraphysiological steroid hormone concentrations. In patients undergoing IVF, gonadotrophin stimulation has been shown to increase oestradiol and testosterone concentrations (Martin et al., 1997). One study showed that testosterone concentrations during stimulation were positively correlated with IVF parameters such as peak oestradiol, follicle number, oocyte number and antral follicle count and was negatively associated with body mass index (BMI) and maternal age (Frattarelli and Gerber, 2006). This same study revealed that testosterone concentrations at any stage in stimulation and even 7 days after stimulation did not predict pregnancy. The only time that testosterone concentrations were different between pregnant and non-pregnant subjects was 14 days after oocyte retrieval, when pregnant subjects had significantly higher testosterone concentrations than subjects who were not pregnant. Although the Fraterelli study indicated that the testosterone concentration was elevated in pregnant women compared with non-pregnant women, the normal range of testosterone in early gestation is unknown. A more recent study (Rashidi et al., 2009) showed a similar finding of testosterone concentration being significantly elevated in pregnant women 14 days after embryo transfer. The available data show that serum testosterone concentrations rise throughout pregnancy, with the peak being in the third trimester, yet little data is available to indicate the normal range at 2 weeks post conception.
The objective of this study was to evaluate testosterone concentrations in early pregnancy in infertile patients who conceived naturally and those who conceived with fertility treatments, including clomiphene citrate, gonadotrophins for ovarian stimulation and insemination and IVF, as well as ovum donation (with recipients undergoing ovarian suppression).
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Materials and methods
This is a prospective cohort study of infertility patients who conceived with or without ovarian stimulation. Serum testosterone concentrations were obtained pre- and post-conception (at 4–6 weeks of gestation) in 95 infertile controls who conceived spontaneously and 342 subjects who conceived following one of four infertility treatments: clomiphene citrate (n = 69), gonadotrophins with IUI (n = 69), IVF (n = 152) and ovum donation (n = 52). Baseline testosterone concentrations were obtained at the time
Results
Although all groups demonstrated some increase in pregnancy testosterone from baseline concentrations, subjects who conceived following ovarian stimulation showed a significantly higher rise in serum testosterone (ΔT) as compared with controls, (P = 0.028 for clomiphene group and P < 0.001 for both the gonadotrophin and IVF groups) while ovum donor recipients had significantly lower rises in testosterone concentrations in early pregnancy compared with controls (P = 0.003; Table 1). Within each group,
Discussion
Compared with natural cycle conceptions, ovarian stimulation resulted in higher testosterone concentrations during early pregnancy. Not only did the number of eggs retrieved at IVF correlate with pregnancy testosterone concentrations, but recipients of ovum donation had the lowest concentrations, indicating an ovarian aetiology for the excess. Whether ovarian stimulation leads to elevations in pregnancy testosterone concentrations that could potentially impact perinatal outcomes is uncertain.
Acknowledgement
Immulite 2500 testosterone assay kits were donated by Diagnostics Product Corporation.
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Lynn Marie Westphal, MD, FACOG, graduated summa cum laude from Lawrence University in Appleton, Wisconsin, earned her MD degree at Stanford University, and did her residency training in obstetrics and gynaecology at the University of California, Los Angeles and Stanford University. She did a fellowship in molecular biology at Stanford University and completed her fellowship in reproductive endocrinology and infertility at the University of California, San Francisco. She joined the full-time faculty at Stanford University in 1998 and is an associate professor in the department of gynaecology and obstetrics, director of the Fertility Preservation Program, director of the Third Party Reproduction Program and director of the Reproductive Endocrinology and Infertility Fellowship.
