Blood metal/metalloid concentration of male subjects undergoing IVF/ICSI treatment outcomes: A prospective cohort study

BackgroundPrevious epidemiology studies reported that heavy metal/metalloid exposure is associated with the impairment of semen quality. However, it is still not clear whether the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment outcome will be affected after the heavy metal/metalloid exposure of the male partners.MethodsA prospective cohort study with a 2-year followed-up was conducted in a tertiary IVF center. A total of 111 couples undergoing IVF/ICSI treatment were initially recruited from November 2015 to November 2016. Male blood concentrations of heavy metal/metalloid including Ca, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Mo, Cd, Hg, and Pb were measured by inductively coupled plasma mass spectrometry, and the lab and pregnancy outcome data were followed up. The associations between male blood heavy metal/metalloid concentration and the clinical outcomes were analyzed by Poisson regression analysis.ResultsOur results showed that none of the heavy metal/metalloid of male partners we investigated are significantly associated with the oocyte fertilization and good embryo (P ≥ 0.05); however, antral follicle count (AFC) was a protective factor for the oocyte fertilization (RR: 1.07, 95 % CI: 1.04–1.10). The blood Fe concentration of the male partner was positively associated (P < 0.05) with pregnancy in the first fresh cycle (RR:170.93, 95 % CI: 4.13–7082.04), cumulative pregnancy (RR: 23.61, 95 % CI: 3.25–171.64) and cumulative live birth (RR: 36.42, 95 % CI: 1.21–1092.54). In the first frozen embryo cycles, pregnancy was significantly associated (P < 0.05) with the blood Mn (RR: 0.01, 95 % CI:0.00–0.11) and Se concentration (RR: 0.01, 95 % CI:8.25 E-5–0.47) and female age (RR: 0.86, 95 % CI:0.75–0.99); live birth was significantly associated (P < 0.05) with the blood Mn concentration (RR: 0.00, 95 % CI: 1.14E-7–0.51).ConclusionsOur results suggested that the higher male blood Fe concentration was positively associated with pregnancy in the fresh embryo transfer cycle, cumulative pregnancy, and cumulative live birth, whereas the higher male blood Mn and Se concentration were associated with lower chance of pregnancy and live birth in the frozen embryo transfer cycle. However, the underline mechanism of this finding still needs further investigation.     

Ablastin: Antigen tolerance and lack of ablastin control of Trypanosoma musculi during host's pregnancy

A short review is given about recent observations of infections in pregnant laboratory mice with strains of Trypanosoma musculi (= T. duttoni) isolated in southern Europe. When being infected during the highly sensitive period of mbryogenesis, the female is completely unable to inhibit the reproduction of the trypanosome. Like an excessively growing benign tumor, the normally well-adapted nonpathogenic blood parasite population becomes, under these conditions, harmful to the host. The placenta acts as a “focus” of the trypanosome reproduction. Unusual, incomplete multiple fissions occur as big rosette formations in the placental blood. The possible microëcological conditions of the accelerated trypanosome growth are briefly discussed. An American strain of this trypanosome species shows the same behavioral pattern in pregnant hosts.     

Trypanosoma lewisi and T. cruzi: Effect of infection on gestation in the rat

Termination of pregnancy occurred in the rat after infection with Trypanosoma lewisi early in gestation. Rats were inoculated on Day 2 of pregnancy and the uteri were excised and examined on Days 10 and 14 of gestation. There were no detectable differences in size in the fetuses of infected and control females at Day 10, but by Day 14 young of infected females were being reabsorbed, and their weight was markedly less than that of control young.A bioassay of estrogens and progestogens based on the decidual cell response indicated that there was a sufficient hormone level to maintain pregnancy beyond Day 10, so the mechanism of action by which fetal death was produced did not appear to be hormone depletion. The crucial changes in fetal weight occurred between Days 12 and 14 of gestation in rats infected with T. lewisi on Day 2 of gestation.Trypanosoma cruzi caused little or no pathologic change in the pregnant laboratory rat throghout the period of gestation and infected females gave birth to apparently normal young.     

Molecular mechanisms of the antihormonal and antiimplantation effects of norethisterone and its a-ring reduced metabolites

Norethisterone (NET) has been used as a contragestational postcoital agent. It is biotrans-formed to 5α dihydro-NET (5α-NET) and 3β,5α tetrahydro-NET (3β,5α-NET) in target tissues. The participation of these metabolites in NET effects is unknown. We have examined the antiimplantation and antiprogestational effects of NET and its metabolites, in adult mated female rabbits, by assessing the number of implantation sites and the expression products of the uteroglobin (UTG) gene in the uterus, and by comparing them with those of RU-486 and estradiol. Steroids were daily administered s.c. at several doses for 7 consecutive days, starting 24 hr after coitus. To assure that fertilization occurred in all animals, the presence of early pregnancy factor was determined. The results demonstrated that high doses (5 mg/kg) of NET reduced both implantation and the expression of the UTG gene. On the other hand, lower doses (1.5 mg/kg) of 5α-NET produced an antiimplantation effect and suppressed UTG synthesis and its mRNA. These effects were similar to those of RU-486. At lower doses (1 mg/kg), both estradiol and the estrogenic metabolite 3β,5α-NET were also effective in inhibiting implantation and UTG gene expression. The overall results suggest that NET metabolites exert antiimplantation and antiprogestational effects through their interaction with progesterone and estrogen receptors, and provide an explanation for the molecular mechanisms involved in the postcoital contraceptive action of NET. © 1995 Wiley-Liss, Inc.     

Pregnancy-induced long-term uterine vascular remodeling in the rat

Despite the available research investigating uterine physiology during and immediately following pregnancy, including at the vascular and muscular levels, knowledge of the potential long-term timeline of such changes is limited. Thus, our study sought to investigate the potential long-term changes in uterine vasculature and horn length in the postpartum rat, following delivery and weaning. Female Long-Evans rats (n = 9–11 rats/group/timepoint) were divided into two groups: a pregnant group and an age-matched virgin control group. Rat weight, food consumption and vaginal impedance measurements were recorded throughout the experiment. Rats in the pregnant group were bred and pregnancy was confirmed using ultrasound imaging. The uterus and its vasculature were collected at various timepoints following weaning: 3 (week of weaning), 8–9 and 13 weeks postpartum, and at age-equivalent timepoints in the virgin group, and the diameters of the main uterine artery and vein, and lengths of the mesometrial segmental vessels (MSV) and uterine horns were recorded. The results indicated a significant difference between the previously-pregnant and virgin rats in both internal and external arterial diameters (but not arterial wall thickness), as well as the uterine horn length, 3 weeks postpartum, but not 8–9 and 13 weeks postpartum. Significant differences were observed in both venous diameter and MSV length at all timepoints measured. Placental scars were also observed in previously-pregnant rats at all timepoints measured. Our study highlights the long-term impact of pregnancy on the uterine vasculature and the necessity for consideration of such changes on subsequent pregnancies, as well as pregnancy-related vascular pathologies.     

Marriage season, promptness of successful pregnancy and first-born sex ratio in a historical natural fertility population – evidence for sex-dependent early pregnancy loss?

 We investigated population-based vital records of the seventeenth and eighteenth century French Canadian population to assess the effects of marriage season on the outcome of the first births under natural fertility conditions (n=21,698 marriages). Promptness of the first successful conception after marriage differed according to marriage season; the proportion of marriages with a marriage-first birth interval of 8.0–10.0 months was lowest (34%) for marriages in August–October (P=0.001). Although the male/female sex ratio of the babies born with an interval of 8.0–10.0 months was generally higher (1.10) than those with an interval of 10.0–24.0 months (1.05), the marriages in August–October resulted in a significantly reduced sex ratio (0.96) among only the prompt conceptions (P=0.026). We discuss whether this seasonal reduction of the sex ratio could be partly explained by a clustered pregnancy loss of male zygotes in early pregnancy. Received: 5 January 1998 / Accepted: 9 September 1998     

Coagulation parameters do not change during luteal phase and pregnancy in cats

Changes in coagulation parameters depending on reproductive status and pregnancy have been previously reported in both human and other veterinary species. The objective of this study was to determine if different reproductive status affects coagulation parameters in queens. Blood samples from 66 queens submitted to spay surgery were obtained. A hemostatic panel including platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen concentration, and D-dimer and also progesterone concentrations were measured before surgery. According to progesterone results and embryo vesicles diameter, four groups were established: (1) nonpregnant queens with low (≤1 ng/mL) progesterone concentration (LP) (n = 33); (2) nonpregnant queens with high (≥2 ng/mL) progesterone concentration (n = 8) (HP); (3) first half of pregnancy (n = 12); and (4) second half of pregnancy (n = 13). None of the evaluated parameters showed statistically significant differences among the different groups. There was no significant linear correlation between progesterone values and coagulation parameters. In conclusion, neither the presence of the embryo nor the higher values of progesterone concentration induced statistically significant changes in the coagulation profile studied.     

Inhibition of mammary tumorigenesis in virgin rats by adoptive transfer of splenocytes from parous donors

Summary Splenocytes from parous rats have been previously found to have cytotoxic activity against mammary tumor cells in vitro. Experiments were carried out to determine if this pregnancy-induced cytotoxic nature of the splenocytes is inherent and transferable. Splenocytes from parous rats were adoptively transferred to a group of virgin rats. Another group of age-matched, virgin rats received splenocytes from virgin donors in a similar way. After a period of rest, at the age of 55 days, the rats belonging to both of the groups, received 7,12-dimethylbenz(a)anthracene (DMBA) intragastrically. A third group of untreated virgin rats were also given the chemical carcinogen the same way as above and were considered as intact controls. The rats were monitored for development and growth of mammary tumor from 60 days of DMBA administration. After 4 months of DMBA administration the rats were sacrificed and mammary glands were examined for tumors. Mammary glands with no visible tumors were taken for whole mount preparation, to be examined for microscopic lesions. The results showed that 33 of 41 intact control rats, developed tumor and 27 of the 34 rats that received spleen cells from virgin rats developed tumors. Of the rats that received spleen cells from parous rats, only 18 out of 37 rats developed tumors, indicating an inhibition of tumor induction in these rats. Growth rate of the tumors in this group was also slower than in the control groups.This research was supported by USPHS grant CA 3613906 awarded by the National Cancer Institute