International Journal of Reproductive BioMedicine
Volume:19 Issue: 6, Jun 2021

Activation of caspase, externalization of phosphatidyl serine, change in the mitochondrial membrane potential, and DNA fragmentation are apoptosis markers found in human ejaculated spermatozoa. Also, reactive oxygen species (ROS) play a vital role in the different types of male infertility. In this review, data sources including Google Scholar, Scopus, PubMed, and Science Direct were searched for publications with no particular time restriction to get a holistic and comprehensive view of the research. Apoptosis regulates the male germ cells, correct function and development from the early embryonic stages of gonadal differentiation to fertilization. In addition to maintaining a reasonable ratio between the Sertoli and germ cells, apoptosis is one of the well-known quality control mechanisms in the testis. Also, high ROS levels cause a heightened and dysregulated apoptotic response. Apoptosis is one of the well-known mechanisms of quality control in the testis. Nevertheless, increased apoptosis may have adverse effects on sperm production. Recent studies have shown that ROS and the consequent oxidative stress play a crucial role in apoptosis. This review aims to assimilate and summarize recent findings on the apoptosis in male reproduction and fertility. Also, this review discusses the update on the role of ROS in normal sperm function to guide future research in this area.

Fetal growth is determined by the interaction between mother and fetus using the placental interface throughout the pregnancy.

To research apoptosis and appearance of hepatocyte growth factor (HGF) in placentas of different gestational ages and to describe the anthropometrical and clinical indices of mothers and newborns.

The study material was obtained from 53 human immunodeficiency virus negative pregnant women of legal age without systemic diseases. The staining of placental apoptotic cells was processed by a standard in situ cell death detection kit. The detection of HGF was provided by the ImmunoCruz goat ABC Staining System protocol sc-2023. Relative distribution of positive structures was evaluated using the semiquantitative counting method.

The mean rank value of the amount of HGF-containing cells (cytotrophoblasts, syncytiotrophoblasts, extravillous trophoblasts, Höfbauer cells, and cells of extraembryonic mesoderm) was 1.61 ± 0.94. Apoptotic cells (cytotrophoblasts, syncytiotrophoblasts, extravillous trophoblasts, and cells of extraembryonic mesoderm) were found in all placental samples of various gestational ages (term 13.00 ± 13.05 and preterm 27.00 ± 18.25); in general, their amount decreased with advancing gestational age of the placenta (p < 0.01).

Weight of a placenta directly depends on the gestational age and correlates with the main fetal anthropometrical parameters (weight, length, and head and chest circumferences). The decrease in HGF-containing and apoptotic cells with advancing gestation depends on the adaptation potential of the placenta, proving the other ways of cellular disposition.

Polycystic ovarian syndrome (PCOS) is an endocrine and complex metabolic disorder, associated with anovulation, changes in sex hormone, biochemical factors, and ovarian tissue. Royal jelly (RJ) has antioxidant and anti-inflammatory properties.

To examine the therapeutic effect of RJ on PCOS-related hormonal and biochemical changes in a rat model of PCOS.

In this experimental study, 42 female Wistar rats (weighing 180-200 gr, aged 10-12 week) were divided into six groups (n = 7/each): control; PCOS; RJ 100 mg/kg; RJ 200 mg/kg; PCOS + RJ 100 mg/kg; and PCOS + RJ 200 mg/kg. After 21 days, the animals were weighed and dissected. The serums were used for nitric oxide (NO) and ferric-reducing antioxidant power (FRAP) assay and estradiol and progesterone measurements. The ovaries were assessed for histological changes.

PCOS increased estradiol and NO levels, and decreased progesterone and FRAP levels. In PCOS+ RJ groups, the progesterone (p  =0.01) and FRAP levels (p ≤ 0.001) increased and the estradiol and NO (p ≤ 0.001) levels decreased significantly. Moreover, the number of mature follicles (p = 0.01) and corpus luteum increased (p ≤ 0.001), and ovarian and uterus weight deceased significantly (p ≤ 0.001).

RJ improved estradiol, progesterone, FRAP, and NO levels, and ovarian structure in the rat model of PCOS.

Excessive consumption of alcohol induces an increase in oxidative stress production and can lead to detrimental effects on the male reproductive system.

To evaluate the possible protective effects of co-administration of vitamin (vit) E on the detrimental changes in the sperm quality of mice administered ethanol.

Fifty-four BALB/c mice were categorized into nine groups (n = 6/each). The control group received a basal diet while the eight experimental groups received ethanol 10%; ethanol 20%; vit. E 100 mg; vit. E 200 mg; ethanol 10% + vit. E 100 mg; ethanol 10% + vit. E 200 mg; ethanol 20% + vit. E 100 mg; ethanol 20% + vit. E 200 mg. After 35 days, the sperm parameters and sperm chromatin were assessed.

The results demonstrated a significant reduction in the motility rate, normal morphology rate, viability rate, increase in abnormal DNA structure and packaging (TB staining), and DNA damage (TUNEL) in ethanol consumer groups. In addition, the findings showed a significant increase in the aforementioned parameters in ethanol- and vit. E-consumer groups compared to the ethanol-only consumer groups. The ethanol group received 20% of the most damage among the groups. The group receiving vit. E 100 mg and those receiving ethanol 10% + vit. E 200 mg gained the highest benefit among the groups.

Sperm forward progressive motility, normal morphology rate, and viability decreased in the ethanol groups. Also, the rates of spermatozoa with abnormal DNA structure and DNA fragmentation increased in the ethanol groups. Our findings revealed that the co-administration of vit. E and ethanol can protect destructive changes in DNA structure and damage.

Various strategies have been proposed for polycystic ovary syndrome (PCOS) treatment.

To investigate and compare the number and size of ovarian follicles, endometrial thickness, and ovulation rate by traditional protocol (TP) and stair-step protocol (SSP).

Sixty infertile PCOS women were allocated into two groups (SSP = 30 and control TP = 30) between May and October 2019 in the Besat Hospital, Sanandaj, Iran. In the SSP group, the infertile women were treated with 50 mg/daily clomiphene citrate (CC) for five days, while the nonresponsive women were prescribed 100 mg daily CC for five days in the same cycle. The maximum dose (150 mg) was administered until ovulation occurred. In the control group, in non-ovulatory cases, the dose was increased in the next cycle. Ultrasound was used to detect ovulation.

Endometrial thickness changes with various doses of CC were significantly different in the TP. The comparison of both protocols showed a significant difference in endometrial thickness only at 50 mg CC. The number of follicles in the left ovary was significantly different in both protocols at 150-mg CC. The size of ovarian follicles in the left ovary was significantly different between the two protocols at 100-mg CC. The ovulation rate was significantly different in the SSP at 100- and 150-mg doses of CC. Moreover, 86% of ovulation occurred at 100-mg CC in the SSP, while this rate was 73% in the TP.

The most appropriate dose for ovulation in patients with PCOS is 100 mg CC.

Oxidative stress is caused by the imbalance occurring between the creation and clearance of the reactive oxygen species (ROS), which is responsible for 30-40% of male infertility. The positive impact of phoenix dactylifera pollen (Date palm pollen, DPP) on the improvement of sperm parameters has been well documented in animal models.

For evaluating the effect(s) of DPP on sperm parameters, ROS levels, expression of antioxidant genes, and activity of antioxidant enzymes of infertile men.

In this controlled clinical trial, a total of 60 male case with infertility and 20 normospermic fertile men were recruited. Before and after the treatment with DPP, the case were administered 400 mg/kg of gelatinous capsules daily for 30 consecutive days and semen samples were taken. Quantitative real-time polymerase chain reaction was applied for the evaluation of the mRNA expression levels of Nuclear factor erythroid 2-related factor 2 (NRF2), superoxide dismutase (SOD2), glutathione peroxidase 4 (GPX4), and catalase (CAT) genes.

The mRNA expression levels of NRF2, SOD2, GPX4, and CAT (p < 0.05 for all) and significantly increased after treatment with DPP. The increased expressions of all antioxidant genes and enzymes significantly correlated with improvement in semen parameters including count (p = 0.01), motility (p = 0.05), and morphology (p = 0.01) of sperm. A significant correlation between the alteration of SOD2 gene expression and SOD activity, GPX4 and GPX, and CAT were also observed (p = 0.05).

DPP can increase the expressions of NRF2, GPX4, SOD2, and CAT genes and also improve the semen quality in infertile men.

Recurrent pregnancy loss (RPL) refers to the incidence of two or more abortions before the first half of pregnancy. Oxidative stress has been hypothesized to play a central role in RPL.

To investigate the relationship between Q192R and L55M polymorphisms of PON1 as antioxidant enzyme and the risk of RPL.

In this case-control study, 110 women with RPL (case) and 110 healthy fertile women (control) referred to the Research and Clinical Center for Infertility, Shiraz, Iran were enrolled. Genomic DNA was extracted from the peripheral blood in all participants. Polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism method.

Statistical analysis of Q192R polymorphism showed a significant difference for the RR genotype between the case and control group (OR = 11, CI = 1.39-86.87, p = 0.005) but none for the QR and QQ genotypes. No significant association was observed between the R and Q allelic frequency in the RPL participants compared to the control group (p = 0.53). Also, statistical analysis of the L55M polymorphism for MM genotype in the case group compared with the control group showed a significant difference (OR = 3.59, CI = 0.97-13.30, p = 0.042), but none for the LM and LL genotypes.

The findings showed a significant correlation between the Q192R polymorphisms and the L55M PON1 enzyme and RPL in this study population.

Some women represent the inability to respond to endogenous and exogenous gonadotropins during in vitro fertilization/intracytoplasmic sperm injection cycles leading to the follicular developmental arrest. The women with resistant ovaries could benefit from in vitro maturation.

Case report: 

This case-series presents pregnancies resulting from initially scheduled conventional in vitro fertilization which led to arrested cycles because of resistant ovary syndrome. The protocol was changed to early oocyte triggering for 15 women due to the small follicles ≤ 12 mm in diameter on day 15 after stimulation with high doses of exogenous gonadotrophins instead of cycle cancellation. Germinal vesicle and metaphaseI oocytes that were retrieved from follicles were matured in vitro and inseminated by intracytoplasmic sperm injection. Twenty formed embryos were transferred on day 3 after oocyte retrieval. This resulted in a 30.76% chemical pregnancy out of which no abortion occurred. Therefore, we reported a 30.76% singleton ongoing pregnancy.

It seems that early oocyte triggering followed by in vitro maturation may be considered as a good modality in women experiencing follicular resistance to gonadotropins. These cycles can be rescued from cancellation with satisfactory clinical outcomes.

The authors regret that the start date of the study was published incorrectly (Pages 671 and 672). The start date must be changed from August 2018 to May 2018. The authors would like to apologize for any inconvenience caused. The online version of article has been updated on July 14, 2021.