International Journal of Reproductive BioMedicine
Volume:20 Issue: 8, Aug 2022

Prenatal diagnosis of hereditary diseases has substantially altered the way medical geneticists are helping families affected by genetic disorders. However, the risk of miscarriage and fear of invasive diagnostic procedures may discourage many couples from seeking prenatal diagnosis. With the discovery of maternal plasma cell-free fetal DNA, prenatal diagnosis has entered a new era of progress. Cell-free DNA is released during normal physiological functions as well as through the cell death programs of apoptosis and necrosis. It can be found in the plasma and other body fluids. Although this method has the advantage of being noninvasive, it is still rather expensive and requires advanced hardware and comprehensive data analysis. Promising implications of noninvasive prenatal diagnosis methods for the diagnosis of common trisomy disorders have paved the way for the development of more complicated assays of single-gene disorders. Relative mutation dosage and relative haplotype dosage are the most widely implemented assays for noninvasive prenatal diagnosis of single-gene disorders. However, each assay has its own advantages and disadvantages. Relative mutation dosage is based on the droplet digital polymerase chain reaction (PCR) technique which includes quantification features of real-time PCR assays. Relative haplotype dosage is based on next-generation sequencing that includes analysis of the maternal and paternal genome followed by sequencing of maternal plasma cell-free DNA. Co-amplification at a lower denaturation temperature PCR is another approach that is based on forming heteroduplexes between alleles to selectively amplify paternal mutations. In this review, we have described the most common noninvasive prenatal diagnosis approaches and compared their applications in genetic disorder diagnosis with different inheritance patterns.

Amniotic fluid (AF) is a clear yellow fluid that surrounds the fetus during pregnancy. The amniotic sac consists of 2 layers: the amnion and the chorion. Osmotic and hydrostatic forces cause the maternal plasma to pass through the fetal skin and generate the AF. AF allows the fetus to grow inside the uterus, supports it from injuries, retains consistent pressure and temperature, and enables the exchange of body chemicals with the mother. At first, it consists of water and electrolytes but after the 12-14th wk the liquid also contains carbohydrates, proteins, lipids, phospholipids, urea, hormones, and some biochemical products. AF appearance is characterized by the grade of cloudiness and the number of flakes of the vernix. The volume of AF increases with the fetus's growth. Its appearance depends on the gestational age. In addition to differentiated cells, stem cells are also found within the AF. These cells express embryonic-specific cell markers and bear high self-renewal capacity and telomerase activity. AF stem cells possess the potential to differentiate into osteogenic, cardiac, skeletal muscle, lung, neuronal, kidney, bone, cartilage, ovarian and hepatic cells in vitro. They represent a great promise in regenerative medicine for the reconstruction of bio-artificial tissues and organs in vivo. The purpose of this paper was to briefly review the development and function of AF and the application of its stem cells in cell therapy.

Myo-inositol is an intracellular mediator which is involved in various aspects of reproduction in women.

This study aimed to evaluate the impact of Myo-inositol on the outcomes of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles in infertile women.

This double-blind randomized controlled trial was conducted on 70 infertile women referred to the Infertility Treatment Center, Besat hospital, Sanandaj, Iran from May 2019 to September 2019 for IVF/ICSI cycles. The participants were randomly divided into 2 intervention (n = 36) and control (n = 34) groups. The intervention group received 2000 mg of Myo-inositol and 200 mcg folic acid twice a day for 2 months and the control group received 200 mcg of folic acid twice a day for 2 months in the IVF/ICSI cycles (from the third day of cycle until the end of the second month). Finally, the number of oocytes, the quality of embryos, and the IVF/ICSI outcomes were compared between the 2 groups.

The mean numbers of oocytes, MII oocytes, and 2 pronuclear embryos were significantly higher in the intervention group than the control group. Also, the clinical pregnancy and live birth rates in the intervention group were significantly higher than in the controls (p = 0.04).

The administration of Myo-inositol may increase clinical pregnancy and live birth rates by increasing the number of total and meiosis II oocytes in infertile women undergoing IVF/ICSI.

Cyclophosphamide (CP) is an anticancer agent, but its chronic administration induces ovarian toxicity.

We evaluated the effects of aqueous extract (AE) and methanol extract (ME) of Amaranthus hybridus (A. hybridus) on CP-induced ovarian toxicity in rats.

40 female Wistar rats (10 wk, 170-200 gr) were distributed into 8 groups (n = 5/each) as follows: 1) healthy control; 2) CP+distilled water (10 ml/kg/d); 3) CP+3%-tween 80 (10 mL/kg/d); 4) CP+clomiphene citrate (2 mg/kg/d); 5, 6) CP+AE of A. hybridus (55 and 110 mg/kg/d); and 7, 8) CP+ME of A. hybridus (55 and 110 mg/kg/d). After 28 days of treatment, estrus cyclicity, ovarian and uterine weights as well as estradiol levels and ovarian histology were determined.

CP induced ovarian toxicity after 28 days of exposure. More specifically, CP disturbed the estrus cycle, decreased ovary and uterus weights (p = 0.04), and the 17-β estradiol level (p = 0.04), and induced severe ovarian damages. Remarkably, A. hybridus significantly increased (p = 0.03) the ovarian weight (AE and ME at all doses) and uterus weight (ME at 110 mg/kg/d), compared with the CP-treated rats. Moreover, the 17-β estradiol level was significantly elevated (p = 0.02) in rats given clomiphene citrate and A. hybridus (AE 110 mg/kg/d; ME 55 mg/kg/d). Finally, the ovaries of rats given plant extracts had many corpus luteum and normal follicles, and no cystic follicles.

A. hybridus prevented the detrimental effects of CP on ovarian function, which could support its traditional use as a fertility enhancer.

The cerebroplacental ratio (CPR) is an important factor for predicting adverse neonatal outcomes in appropriate-for-gestational-age fetuses.

To evaluate whether there is an association between the CPR level and adverse neonatal outcomes in appropriate-for-gestational-age fetuses.

This cross-sectional study included 150 low-risk pregnant women candidates for elective cesarean sections at the gestational age of 39 wk. CPR and middle cerebral artery pulsatility index (MCA PI) were calculated in participants just before cesarian section. Postnatal complications were defined as an adverse neonatal outcome such as an Apgar score of the neonate ≤ 7 at 5 min, neonatal intensive care unit (NICU) admission, cord arterial pH ≤ 7/14, and meconium stained liquor.

The mean age of participants was 31.53 ± 4.91 yr old. The mean CPR was reported as 1.83 ± 0.64. The Chi-square test analysis revealed that a low MCA PI and a low CPR were significantly associated with decreased cord arterial pH, decreased Apgar score at 5 min, and NICU admission (p < 0.001). There was no significant association between umbilical artery PI with arterial cord pH, Apgar score at 5 min, NICU admission, or meconium stained liquor. The Mann-Whitney test showed that a lower fetal weight appropriate for the women’s gestational age was significantly associated with a decreased CPR and MCA PI (p < 0.005). There was no significant association between amniotic fluid index and CPR, umbilical artery PI, or MCA PI.

The CPR is a significant factor in predicting adverse neonatal outcomes and ultimately neonatal mortality and morbidity of low risk, appropriate-for-gestational-age fetuses.

It is estimated that 1-5% of couples suffer from recurrent pregnancy loss (RPL). Recent studies have shown the effects of gene polymorphisms in RPL.

The aim of this study was to evaluate 3 gene polymorphisms including rs1048943 of CYP1A1, rs28371725 of CYP2D6, and rs7830 of NOS3 in idiopathic RPL to identify their association with RPL.

Blood samples were collected from 136 women with at least 2 consecutive idiopathic miscarriages (case group) and 136 women with no history of miscarriage and at least one successful pregnancy (control group) from the Iranian Azeri population. This study was carried out between April 2018-April 2020. Amplification-refractory mutation system polymerase chain reaction was used for the rs7830, rs1048943 and rs28371725 polymorphisms in order to genotype each extracted genomic DNA sample. After that, Chi-square, Fisher’s exact test and logistic regression were used to investigate whether each of these polymorphisms is associated with RPL.

Among these polymorphisms, only rs1048943 of CYP1A1 showed a statistically significant association with RPL in the Iranian Azeri women studied.

Our results suggest that CYP1A1 gene polymorphisms might be associated with a reduced risk of RPL. Further studies in other populations and in the same population with a larger sample size, as well as functional genomics analyses such as gene expression analyses or epigenetic studies are required to validate our results.

The miscarriage rate after pregnancy resulting from assisted reproductive technology (ART) is about 20%, roughly half of which is biochemical. The correlations between the number and quality of oocytes, estradiol level and early pregnancy loss have not been fully clarified.

This study aimed to examine the clinical and laboratory parameter effects on early abortion in ART cycles.

In this cross-sectional study, 408 women who were ART candidates and were referred to the Yazd Infertility and Research Center, Yazd, Iran during March 2017 to March 2020 participated. Women who had a fresh embryo transferred and who had a positive beta human chorionic gonadotropin serum test were included in the study. The Anti-Müllerian hormone (AMH) level, embryo quality, oocyte number, progesterone level, estradiol level, and maternal age were extracted from the medical records.

No significant difference was observed in the age, mean estradiol and progesterone levels on trigger day, number of MII oocytes, and embryo quality between the groups (p = 0.19, 0.42, 0.07, 0.34 and 0.20, respectively). No statistically significant difference was found between the 3 groups of AMH level (p = 0.20). After evaluation using logistic regression, the rate of negative clinical pregnancies was higher in the group with AMH < 1 ng/ml. However, this was not found to be statistically significant.

We did not find any correlation between early abortion and AMH levels, embryo quality, oocyte number, progesterone level, estradiol level, or maternal age.

Endometriosis is believed to be associated with dysfunction of the lymphocyte population and cytotoxicity of natural killer (NK) cells, induced by the production of interleukin-2 (IL-2).

This study aimed to investigate T lymphocytes and NK cell activity in the peripheral blood mononuclear cells (PBMCs) of women with endometriosis.

PBMCs were obtained from the peripheral venous blood samples of 14 women with and without endometriosis (n = 7 for each group). Then, the PBMCs were co-cultured for 4 days and were treated with recombinant IL-2 for cytotoxic activity toward target cells (Daudi and K562 cells). The cytotoxicity activity was determined using the 51 chromium release assay before and after stimulation. Flow cytometry measurement was used to examine the expression of T lymphocytes and NK cells before and after being treated with IL-2.

The concentration of CD3+CD28+ (co-stimulatory) was significantly lower in the endometriosis group (65.62 ± 5.38) compared to in its counterpart (50.24 ± 4.22) (p = 0.04) before stimulation. However, no significant differences were observed in any other T lymphocytes and NK cells. It was also found that there was a significant increase of CD3-CD28+ after treatment with IL-2 only in the healthy control but not in women with endometriosis.

Increased expression of CD160 and decreased CD28 play a role in inhibiting NK cell activation and T cell response in women with endometriosis.