Journal of Reproduction & Infertility
Volume:20 Issue: 2, Apr-Jun 2019

Surrogacy is one of the assisted reproduction methods which have a very long history. The first traditional surrogacy was performed in about 2000 years before the birth of Christ as mentioned in the Holy Qur'an of Muslims and the Christians Bible; Sarah was the wife of Abraham prophet and she was sterile which made her unable to conceive.  Hajar was a female servant of Sarah who asked to carry a child for Abraham prophet. Afterward, Hajar delivered a son for Sarah named Ishmael. This is the traditional, genetic or partial form of surrogacy; it has already been performed by artificial insemination of the surrogate with sperm of intended father and the usage of this form of surrogacy has been greatly reduced. This surrogate mother not only carries the embryo till full term delivery but also provides the eggs that make her a genetic parent. Moreover, the most popular form is gestational, or IVF surrogacy in which an embryo from the intended parents, or from a donated oocyte or sperm, is transferred to the surrogate’s uterus. In gestational surrogacy, the mother who carries and delivers the child (the gestational carrier) has no genetic relation with the child (1).
Surrogacy is used for approximately 2% of embryo transfer cycles in USA. The indications for surrogacy include absence of the uterus, recurrent pregnancy loss, repeated IVF failure, poor obstetric history, contraindication of pregnancy, excessive maternal risk, etc. Surrogacy improves pregnancy and live birth rate   compared to otherART cycles without surrogacy.  The best results are observed in surrogate candidate due to uterine factor infertility (2).
Most of the studies reported better prenatal outcomes in surrogacy including   hypertension, preeclampsia, gestational diabetes, placenta previa, preterm labor and lower birth weight in comparison to IVF cycles of their own uterus. However, when these adverse outcomes in surrogate mothers were compared with the same surrogate mothers who became pregnant through spontaneous conception, IVF manifested most of the above adverse outcomes due to laboratory manipulation of gametes and embryos and uterine milieu changes in stimulation cycles (3).
The surrogacy needs IVF facilities without considering infertility etiology, so gestational carriers experienced embryo transfer, pregnancy, successful ongoing pregnancy and delivery. Therefore, precise medical, psychological and social assessments are necessary to succeed in gestation and delivery. Health status of carriers during gestation could affect future health and wellbeing of the child. The history profile of surrogate should contain at least one uncomplicated pregnancy, although not more than 5 deliveries or 3 caesarean sections (4).In spite of most benefits of surrogacy and also considering the fact that it may be the only option for many couples to have a child from their own gametes, surrogacy is prohibited in many European countries such as Germany, Sweden, Norway, and Italy. Due to financial payments and maintaining the dignity and rights of individuals, any payment to surrogate is officially forbidden in many other countries and only compensation of pregnancy-related costs is accepted in Australia, UK, and in many states of USA. Commercial surrogacy is accepted in India, Ukraine, USA and Middle East countries. One of the remarkable cases is accompaniment of surrogacy with oocyte donation cycles, so that 46% of surrogacy cycles in the USA involve donor eggs. Oocyte donation by carrier for intended parents is prohibited in almost all countries (4).
All of these strict regulations have been set up to protect the rights of the parties involved in this sensitive and complex process, including child, surrogate and intended parents. Inappropriate practice of surrogacy in   cases without medical indication such as celebrities, businesswomen and female politicians for the birth of their child in developed countries is another concern of the field. Cross-border commercial surrogacy in poor developing countries such as India, Nepal, Thailand, and Mexico is another concern. Therefore, in spite of the importance and critical role of surrogacy in assisted reproduction technologies and its existence as the only option for many couples in childbearing age, it requires more consideration and more strict regulation at global level compared to current status due to misuse of the practice in unnecessary cases.

Infertility is a major health issue worldwide. Males and females contribute equally to this problem. Diagnostic semen analysis fails to identify 50% of male infertility disorders. In this regard, metabolomics as a new field of omics has been suggested to have the potential of solving and diagnosis of the male infertility problems. Metabolome has a history of around 20 years. However, there are only limited metabolomics studies carried out regarding male infertility. In this review, the current metabolomics researches that have been done in infertile men were reviewed. Based on our own results, using human seminal plasma for metabolomics studies is highly recommended to find potential biomarkers and developing diagnosis tests for detection of main deficiencies in infertile men.

The purpose of this study was to analyze the expression level of CRISP2, CATSPER1, PATE1 and SEMG1 genes in the sperm of men with asthenozoospermia (AZS). AZS is a cause of infertility in men in which the motility of the sperm is reduced. So far, a few genes have been associated with AZS; however, in most of the cases, its molecular etiology is unclear. A total of 35 subjects with idiopathic AZS and 35 fertile and healthy men as control were included. In study after total RNA extraction and cDNA synthesis, relative quantification was performed. B2M was used as the normalizer gene and fold change was calculated by 2−ΔΔCt</sup>method. Mann-Whitney test was used to compare the expression levels between the case and control groups with significance level of p<0.05. Our results showed that CRISP2 (p=0.03) and SEMG1 (p=0.03) were significantly down- and up-regulated in AZS men respectively compared to the controls. But CATSPER1 and PATE1 did not show significant changes. Down-regulation of CRISP2 and up-regulation of SEMG1 were associated with AZS, which could be suggested as the potential candidate genes for the development of a diagnostic marker or potentially for more studies for treatment of AZS.

The role of acquired thrombophilia has been accepted as an etiology of recurrent miscarriage (RM); however, the contribution of specific inherited thrombophilic genes to this disorder has remained controversial. An increased incidence of RM has been suggested in women with inherited thrombophilia.  In this prospective study, assisted women with RM or repeated implant failure (RIF) were subjected to Thromboincode analysis, in order to identify 12 genetic variants for Factor V Leiden, Factor V Hong Kong, Factor V Cambridge, FII, FXIII, FXII, and A1 carriers. Patients included in this study were separated in RM cases (n=43), RIF cases (n=36) and RIF+RM (n=76). As a control group, patients undergoing IVF treatment (n=34) were used and a previously described 249 cases population as a representative sample of Spanish population were selected. Level of statistical significance was p<0.05 and groups were compared by Fisher test, except for age that was compared by t-test. Regarding FXIII, higher values were observed in RM (69.76%), RIF (70%) and in RM+RIF (68.42%) group when compared with our control group (52.94%) and general Spanish population (56.5%), but these differences were statistically significant only in RIF group (p=0.043, p=0.01). Concerning our findings, both RM and RIF patients had a very similar panel of thrombophilia polymorphisms, suggesting that, in both, thrombophilia might have an important contribution. High frequency of Val34Leu polymorphism in RM/RIF presumably speaks in favor of a multifactorial RM genesis, wherean altered thrombophilia status plays a role.

In this study, an attempt was made to validate the use of OSI as a measure of ovarian response during IVF treatment and to correlate OSI with age and BMI and other measures of ovarian response such as AMH, antral follicle count (AFC), total dose of administered gonadotrophins, and duration of stimulation. This study was a retrospective comparative cohort one. The study included a total of 2150 women who underwent the first IVF cycle between January 2008 and December 2017 at our center using long-agonist protocol. Patients were divided into four subgroups according to the circulating AMH level: below the 25th percentile (AMH 0.25-1.1 ng/ml</em>, subgroup A), between 25th and 50th percentiles (AMH 1.2-1.6 ng/ml</em>, subgroup B), between the 50th and 75th percentiles (AMH1.7-2.6 ng/ml, subgroup C), and above the 75th percentile (AMH 2.7-8.5 ng/ml</em>, subgroup D). Qualitative data were analyzed by Chi-square or Fisher’s exact test. The p<0.05 was considered statistically significant. The four subgroups formed on the basis of the AMH level did not significantly differ for age, BMI and infertility duration. OSI was significantly correlated to age (r=0.167; p=0.001), and has negative correlation with AFC (r=-0.236, p=0.001) and AMH levels (r=-0.123, p=0.001). Multiple linear regression analysis was done on OSI with other independent variables such as age, BMI, AFC, AMH. Analysis showed that approximately 8% variation in the value of OSI can be attributed to these variables with the highest correlation with antral follicle count. The present study showed that OSI appears to be a highly reliable index of ovarian responsiveness to recombinant FSH and can be useful to estimate the FSH dose.

A reduction in intra-ovarian vascular resistance is necessary to achieve pregnancy in a natural cycle. The aim of this RCT was to detect whether a vasodilator calcium channel blocker, amlodipine, could increase the pre-ovulatory follicular blood flow, enhance follicular maturation in women with PCOS and improve ovulatory outcome.  Sixty women received induction by clomiphene citrate (CC); thirty were given amlodipine (Amlodipine group) and the other 30 women were given placebo (Placebo group). The pattern of pre-ovulatory follicle blood flow was studied by color and power Doppler ultrasonography pre and post drug administration. Independent t-test was used to compare mean values of the 2 groups. The p<0.05 is considered statistically significant. When comparing the Doppler effect of amlodipine versus placebo in the treatment cycle, it was found that mean value of ovarian arteries (OA) pulsatility index was lower in amlodipine group but it didn't reach statistical significance (p=0.063); however, the mean value of OA resistance index reached statistical significance (p=0.028) in amlodipine group. Moreover, in the second cycle, endometrial thickness was significantly higher (p=0.006) in women of the amlodipine group when compared to those of the placebo group. At least one sonographically detectable mature follicle (≥18 mm</em>) was observed in 54.5% (36/66) during the first cycle. At the second cycle, this proportion significantly rose to 86.7% (26/30) in the amlodipine group, but marginally and non-significantly to 56.7% (17/30) in the placebo group.  Amlodipine as calcium channel blocker was proved to have a role in improving ovarian blood flow at the time of ovulation and enhancing follicular maturation and thus, it may increase the chances of conception.

Male infertility is defined as a man lost his ability to fertilize a fertile female naturally. Diagnosis of male infertility cannot be made just according to basic semen analysis. It is necessity to have specific tests for evaluation of chromatin integrity. In this study, an attempt was made to evaluate the sperm chromatin quality in fertile men and infertile subgroup. Among 1386 couples, 342 men were categorized into normospermia and 1044 were infertile and they were referred to Yazd Research and Clinical Center for infertility treatment. Standard semen analysis and sperm nuclear maturity tests including aniline blue (AB) and toluidine blue (TB) staining were done. Data were analyzed by SPSS software. The p≤0.05 was considered statistically significant. The mean value of TB staining was significantly higher in infertile group compared to normospermic group (p=0.005). Mean of sperm normal morphology was lower in idiopathic infertile men in comparison with normozoospermic men (p=0.001). The highest negative correlation was obtained between sperm count and AB staining. Progressive motility was negatively correlated with AB and TB staining in both groups but there was no significant difference between AB staining and progressive motility in men normospermia group. Sperm chromatin staining using AB and TB showed a negative association between sperm chromatin condensation with sperm count, normal morphology and progressive motility. It seems that the AB and TB test may be useful for the assessment of male fertility potential.

The risk of a woman in a developing country dying from a maternal-related cause is higher compared to a woman living in a developed country. Despite the fact that delivery care service utilization is essential for further improvement of mothers and newborns, the coverage of delivery service in Ethiopia is still near to the ground. This study aimed to identify factors associated with home delivery among women in Ethiopia at their last birth. The data was obtained from 2016 Ethiopia Demographic and Health Survey which is the fourth survey. The sample was selected using a stratified, two-stage cluster sampling design and the data was analyzed using mixed effect logistic regression model. A total of 10,622 women were considered in this study and 67.2% of them gave birth at home. The percentage of home delivery at their last birth was high in Afar and Somali region (89.6% and 81.7%, respectively) while only 3.3% women who lived in Addis Ababa delivered at home. Living in rural areas, being uneducated, older age, not watching TV, and being poor are predictors of home delivery at 5% level of significance. There is a need of giving special attention to women living in rural area, women from poor families and uneducated women to decrease home delivery.

Chromosomal abnormalities are a significant cause of human disorders. The characterization of such abnormalities helps in the identification of known/new genes. The purpose of the present study was to identify the cause of miscarriages in a couple by using combined molecular and cytogenetic techniques.  In this study, the clinical, cytogenetic and molecular cytogenetic evaluations were performed on a couple with recurrent miscarriages. Several methods like GTG banding, silver nitrate (NOR) staining, fluorescence in-situ hybridization (FISH) using whole chromosome paint probes (WCP) and bacterial artificial chromosome (BAC) clones were used. The chromosomal analysis on the metaphases revealed a karyotype of 46,XX in the wife and 46,XY,13p+ in her husband. To check the satellites on 13p region, NOR was performed which showed absence of satellites and presence of euchromatic material. On careful analysis, the satellites were observed on 11q terminal region. Thus, a balanced reciprocal translocation was detected which was confirmed by WCP and Acro-P-arm FISH. Fine mapping with BAC clones narrowed down the breakpoint regions. The application of the combined cytogenetic methods especially NOR helped in identification of the balanced reciprocal translocation with subsequent systematic characterization and the breakpoint regions were identified. The characterization of the breakpoint regions helped in identification of the carrier status which further paved the way for understanding the cause of recurrent miscarriages and proper genetic counseling.

In evolutionary theories (Lamarckian and Darwinian), environment and physical changes could be transmitted to the descendants (1). Psychological factors in human beings (2–4) have a negative impact on the germ cells parameters (5). As time goes on, the quality of sperm is deteriorating (5, 6) as well as humanoocyte/egg (7).
A simple change of environment and environmental preconceptional exposure (i.e., diet, physical activity, smoking, alcohol consumption, etc.) affects the functioning of the genes and the phenotype of the next generation through remodeling epigenetic blueprint of spermatozoa (8, 9). Lifestyle and environmental factors influence the sperm and egg which will affect subsequent generations (10–12). Some studies have examined the transmission of specific behavioral and structural adaptations in relation to the stimulus in the nervous system, from parents to their offspring (10, 13).
Effects of psychological and environmental factors on gene expression persist even after the removal of the inducing agent passed on to subsequent generations (14). So, Genetic Memory can be contemplated in two ways (Biology and Psychology) (10, 15). 
Psychological factors which have the impact on fertility are treated in numerous studies on humans (5, 16–18) as psychological stress (7). The life of wars and prisons has an effect on germ cells (Sperm, menstrual irregularity and reproductive function) (7, 19, 20). Men who suffered from anxiety and depression or who have experienced high levels of stress had long-term sperm damage. Stress affects sperm quality over the long term, even slowing down the mental development of offspring. This stress is transmitted from one generation to another and has other perverse effects (21). 
Sperm of obese men have a distinct epigenetic signature compared to lean men. The methylome of spermatozoa is dynamically remodeled after weight loss (22). Paternal nutritional status can directly affect the health of offspring (21, 23), suggesting that an epigenetic inheritance phenomenon acquired by the environment is transmitted by gametes (22). Environmental factors as exercise and nutritional status induce acute changes in DNA methylation profiles in human skeletal muscle and adipose tissue (24–28) demonstrating that environmental factors are reshaping the epigenome of somatic tissues (22). 
The fertility of humans is impacted by myriad factors (Stress, obesity, alcohol and tobacco, seasonal variations, etc.) (28, 30). "Licking" (31), sense of touch and massage can be a great stress reliever, and is very important to emotional health (32), and sexual desire and performance (33). Scientists have found that the process of "Traumatic stress, etc." can be reversed if mice from traumatized lineages are put in "Enriched" environments (34). Psychotherapy could improve psychological and environmental factors and make the environment more positive and richer (35).   
Scientists have reached several conclusions by researching humans; the trauma would thus modify the behavior of the traumatized individual but also those of his descendants since one finds a metabolic modification until the third generation. This would mean that trauma also affects germ cells (Spermatozoa and ova) which are the only biological link between generations (34). A positive and nurturing environment help humans withstand the threat (34, 36). The decrease in anxiety (37), improvement of psychological factors (38) with reduced vulnerability to stress factor and shocks (39) are related to bgetting a pregnancy (5). 
Negative psychological and environmental factors, war, nutritional status, seasonal variations, physical and social environmental factors and stress have many negative consequences and effects on the germ cells. "Enriched" and positive environments can reverse these factors and have positive consequences on the germ cells in individual that could be transmitted to their off spring. The author would like to thank Mr. Ahmad Alsaleh and Mrs. Sabrié Alsaleh, Dr. Ameni Ahmed, and Mrs. Régine Fabien for their participation in giving the counseling. The author declares that he has no competing interest. Author has not received the financial support for research.