Higher urinary bisphenol A concentration is associated with unexplained recurrent miscarriage risk: evidence from a case-control study in eastern China.

BACKGROUND: Evidence about the association between Bisphenol A (BPA) and the risk of recurrent miscarriage (RM) in human being is still limited. OBJECTIVE: We evaluated the association of urinary BPA concentrations with RM in human being. METHODS: A hospital-based 1:2 matched case-control study on RM was carried out in Suzhou and Kunshan in Jiangsu Province in China between August 2008 and November 2011. Total urinary BPA concentrations in 264 eligible urine samples (102 RM patients and 162 controls) were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The Wilcoxon test and conditional logistic regression were used to estimate the differences between the groups and odds ratios (OR) with 95% confidence intervals (CI), respectively. RESULTS: The median ± IQR (interquartile range) (P75-P25) values of non-creatinine-adjusted total urinary BPA levels in the RM patients and the controls were 1.66 ± 3.69 ng/ml and 0.58 ± 1.07 ng/ml, respectively (0.98 ± 2.67 µg/g Cr (creatinine) and 0.40 ± 0.77 µg/g Cr. The adjusted BPA level was significantly higher in the RM patients than in the controls (Wilcoxon test, Z = 4.476, P < 0.001). Higher level of urinary BPA was significantly associated with an increased risk of RM (P-trend < 0.001). Compared to the groups with urinary BPA levels less than 0.16 µg/g Cr, the women with levels of 0.40-0.93 µg/g Cr and 0.93 µg/g Cr or above had a significantly higher risk of RM (OR = 3.91, 95%CI: 1.23-12.45 and OR = 9.34, 95%CI: 3.06-28.44) that persisted after adjusting for confounding factors. The time from recently RM date to recruitment does not significantly influence the urinary BPA level (P = 0.090). CONCLUSION: Exposure to BPA may be associated with RM risk.

Impact of heavy metals on hormonal and immunological factors in women with repeated miscarriages.

In 111 women with repeated miscarriages, the urinary excretion of heavy metals was determined in a challenge test with the chelating agent 2,3-dimercaptopropane-1-sulphonic acid in addition to hormonal, chromosomal, immunological and uterine investigations. The heavy metal excretion was correlated to different immunological (natural killer cells, T cell subpopulations) and hormonal (progesterone, oestradiol, prolactin, thyroid stimulating hormone) parameters. We conclude that heavy metals seem to have a negative impact on ovarian as well as on pituitary function. The heavy metal-induced immunological changes may interfere with the physiological adaptation of the immune system to the state of pregnancy with the result of a miscarriage. The observed heavy metal-induced hormonal and immunological changes may be important factors in the pathogenesis of repeated miscarriages.

Thromboxane dominance and prostacyclin deficiency in habitual abortion.

To evaluate the significance of vasoactive prostanoids in habitual abortion, we measured urinary excretion of prostacyclin metabolites (6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha) and of thromboxane A2 metabolites (TxB2 and 2,3-dinor-TxB2) during 25 pregnancies in 22 women with recurrent spontaneous abortion (RSA). The control group were 16 pregnant women with no history of abortion. Ultrasound examination at first follow-up appointment showed a living fetus in 23 pregnancies of women with RSA. 9 of these pregnancies ended in abortion; 14 continued to term as did all the pregnancies in the control group. Compared with controls, women with RSA had a lower (p less than 0.05) ratio of prostacyclin to thromboxane between weeks 4 and 7 of gestation and a lower (p less than 0.01) output of 2,3-dinor-6-keto-PGF1 alpha between weeks 8 and 11. Women whose pregnancies ended in abortion had higher (p less than 0.05) output of 2,3-dinor-TxB2 between weeks 4 and 7 of gestation and lower (p less than 0.01) excretion of 2,3-dinor-6-keto-PGF1 alpha between weeks 8 and 11 compared with women whose pregnancies proceeded to term. We conclude that deficiency of vasodilatory prostacyclin may be a factor in habitual abortion.

Chemical abortion in patients with recurrent fetal loss.

PIP: The incidence of chemical, or pre-clinical, abortion was determined in 10 women on 3 occasions after Day 8 after ovulation with a highly sensitive enzyme immunoassay for beta hCG carboxyterminal peptide. Chemical abortion is defined as occurrence of 0.25 mIU hCG/ml on 3 occasions after Day 8 of ovulation on the basal body temperature chart, but menses occurs on schedule. The subjects were selected from a group of 1120 women with history of repeated spontaneous abortion who had been evaluated at the Keio University Hospital between 1984-1990. These women had an average of 3.22 pregnancies, of which on average 2.9 had ended spontaneously. In 4 of these 10 women hCG was 0.25 mIU/ml in first morning urine, but their menses arrived on schedule, and they had no clinical signs of pregnancy. Levels of hCG were 0.25, or 0.25 mIU/ml less than 3 times in the other 6 women. The normal level of hCG in nonpregnant women was reported to be 0.16 mIU/ml. This is the 1st report of documented chemical abortion in a habitually aborting population.^ieng

Measurement of estrone-3-glucuronide and pregnanediol-3 alpha-glucuronide in early morning urine samples to monitor ovarian function.

The determination of the concentration of estrone-3-glucuronide and pregnanediol-3 alpha-glucuronide has been performed by a chemiluminescent immunoassay in early morning urine samples of 14 normal menstruating women and 11 women affected by luteal phase defect. The early morning urine samples were daily collected for an entire menstrual cycle. We have employed a timed and measured volume collection procedure as correction factor. The integrated values of the hormonal data in definite time intervals were used to create a nomogram. By means of this method, it was possible to completely separate normal from luteal insufficiency subjects and to distinguish two different types of luteal phase defects. Moreover, the same approach was applied to the study of the role and the frequency of luteal phase defect in 15 patients affected by habitual abortion and in 17 premenopausal women who had undergone quadrantectomy for T1a No Mo breast cancer. A luteal phase defect was detected in nine of the aborting patients (60%) and in eight women affected by breast cancer (47%). Finally estrone-3-glucuronide was measured in early morning urine samples of 96 prepubertal and pubertal girls in different pubertal stages and in one patient affected by precocious puberty, before and during an agonist GnRH treatment. The urinary test of ovarian function seems to be suitable for diagnostic purposes and for clinical studies.