- Volume:20 Issue:3, 2019
- تاریخ انتشار: 1398/04/18
- تعداد عناوین: 11
Pages 119-120Globally, more than 7 million live births now result from IVF cycles so that more than 6% of the European births and especially in Denmark about 10% of children are conceived through ART. Compliant with this increment, the infertility treatment using third-party and its success rate are increasing during the past decades. At present, more than 16% of the total IVF cycles, more than 20% of all live births result from oocytes, sperm, embryo donation and gestational carriers in US, so that the third-party IVF cycles are the main infertility treatment for aged couples and the success rate of ART cycles is 39.7% in live birth for third-party compared to 29.6% for autologous cycles (1).
The first sperm donation was performed in 1884 and the first donation of the oocyte was done almost one century later in 1983. Since that time, the most important aspects of third-party reproduction have always been the confidentiality in procedure and anonymity of donors. In that era, IVF clinics refused to disclose identity of donor and recommended to recipient couples not to disclose the usage of embryo or gamete donation to their children. Over the centuries, the same tendency and practice were common for adoption. Few parents left a child for adoption namelessly–so that the child and her/his adoptive couple had no data and background about abandoned child (2).
Anonymity is a multifaceted concept which is rarely continual and absolute. Anonymity expresses the rights and privacy of both donors and recipients. However, every child has a right to identify their biological parents and it should be regarded that these children never submit a consent form for their everlasting anonymity, and most of them will try to find their genetic parent in the future. But the rights, interests and privacy of other players of this scene (parents and donors) should not be ignored.
The widespread expansion of genetic databases is generally accompanied with the risk of identification of formerly anonymous donors. Voluntary DNA testing has been entirely common in recent years and so several huge genetic databases covering millions of genetic profiles are available worldwide. Although about 10 companies and websites collect biological samples and offer genealogy services, there is over 100 online DNA databases on medical DNA testing that most of them are available to community (3).
The ease of access to DNA ancestry and genealogical tests will change the concept of anonymity so that even the privacy of people who did not register may be threatened through searching in these accessible genetic databases. It is obvious that adoption facilities and IVF clinics active in donation should urgently change their guidelines, procedures, documents and counseling with donors and recipients to remove the word "anonymous" and substitute it with phrases and content that precisely describe the new situation for possible identification of anonymous donors and donor-conceived children in the future more easily and rapidly.
Accordingly, several countries such as Sweden as the pioneer and subsequently Austria, Finland, Iceland, Netherlands, Switzerland, UK, New Zealand and Australia removed donor anonymity. Following this change of approach, donation fee increased and the tendency to donation was slightly reduced and also the demography of donors has now shifted from young students to older men (2, 4).
This legislation allowed donor-conceived children to apply for identification of their donor through the court at legal age. Although the goal of anonymity is to protect the right of the donor, but donors should understand the possible short and long-term consequences of their donated gift. Although IVF clinics can still claim to keep secret the information of their donors from recipients and donor-conceived offspring, but the clinics have no authority on future facilities and technologies that allow us to search for genetics identity of individuals (4).
In this regard, the first DNA registry (UK donor link, UKDL) for all parties of donation (donor and donor offspring) was established in UK in 2004 for identification of each other through voluntary sharing of their complete data (5).
In the current situation, without DNA testing, they can be identified through DNA matching of their relatives who had DNA testing. At present, age, sex, and contact information of everybody are enough to find their DNA data in genetic databases.
This availability of DNA databases and genealogical tests enhances the risk to the accidental disclosure of donor or donor conceived children. Therefore, disclosure of biological heritage of donor conceived children is now considered a right in most countries. So many active groups support parents for disclosing the origin of donor conceived children at an early age to decrease the risk of accidental identification (2).
Finally, the duty of IVF clinics is very significant in counseling and advising infertile couples and donors about the future potential risks and right of conceived donor children in confronting with biological and legal parents. They should be correctly advised on privacy violation of all parties in the era of DNA ancestry and genealogical testing. Therefore, the donors who cannot accept the potential risk in the future should not be the donors whatsoever.
Pages 121-126BackgroundFor improving the evaluation of male infertility, many parameters were studied and reported in earlier literature. The aim of this study was to estimate the frequency of sperm aneuploidy and DNA fragmentation in infertile men and to assess the correlation between sperm aneuploidy and DNA fragmentation.MethodsIn this study 100 infertile men were included, cases with azoospermia were 68%, oligospermia 18%, severe oligospermia 6%, and oligoasthenoteratospermia (OAT) 8%. Ten normozoospermic men who had two normal children were included as a control. The sperm aneuploidy test by Fluorescence In Situ Hybridization (FISH) and sperm DNA fragmentation index by TdT (Terminal deoxynucleotidyl transferase)-mediated dUTP nick end labelling (TUNEL) were carried out. To determine the aneuploidy status and DNA fragmentation index, frequency was used. The correlation between sperm aneuploidy and sperm DNA fragmentation along with age was assessed by using Spearman's correlation coefficient. The p<0.05 was considered significant.ResultsThe age of 100 subjects ranged between 22-48 years (35.5±5.1). Sperm aneuploidy frequency and DNA fragmentation rate were found to be higher in infertile men compared to control men (n=10). There was a significant relationship between age and sex chromosomal aneuploidy (p<0.05) and significant difference between sperm aneuploidy and damaged DNA (p<0.05).ConclusionFISH and TUNEL assay results showed increased sperm aneuploidy frequency, and DNA fragmentation index in infertile men compared with the fertile men. There is significant relationship observed between sperm aneuploidy and DNA fragmentation. These two parameters are important and they must be investigated for clinical practice.Keywords: DNA fragmentation, Male infertility, Sperm aneuploidy, TUNEL assay
Pages 127-131BackgroundThe evaluation of embryo morphology is one of the most important parameters used to evaluate developmental timing, also providing an indication of chromosomal failure or degeneration. The first step in the evaluation of a fertilization event is determining the number and shape of the pronuclei (PN). Normally fertilized eggs possess two even PN. However, some embryos which develop from abnormally fertilized zygotes may be tri-pronuclear zygotes (3PN).MethodsThirty embryos were collected from 12 women who underwent in vitro fertilization (IVF) at Dr. Cipto Mangunkusumo General Hospital in Jakarta, Indonesia. Embryos were cultured until the blastocyst stage on days 5-6. The blastomere biopsy was performed by piercing the zona pellucida with a laser under a microscope. Chromosomal numerical abnormalities were analyzed using Next Generation Sequencing (NGS).ResultsAmong the 30 embryos with 3PN zygotes, 33.3% had a normal chromosomal array, with 22 pairs of autosomes and 2 pairs of sex chromosomes. While the rest of sample population detected as abnormal chromosome (66.7%), with the highest percentage of abnormality was triploidy 43.3%, followed by mosaicism 13.4% and aneuploidy 10%.ConclusionThis was a preliminary study revealed not all morphologically 3PN embryos are genetically abnormal.Keywords: Aneuploidy, Embryo, IVF, Mosaisicm, Pronucleus
Association Between Sex Steroids and Oxidative Status with Vitamin D Levels in Follicular Fluid of Non-obese PCOS and Healthy WomenPages 132-142BackgroundHuman follicular fluid (FF) is rich in hormones and antioxidants. Many components of FF differ in follicles of patients with polycystic ovary syndrome (PCOS). Regarding vitamin D effects on gene expression, 25(OH)D level of FF and its association with oxidative status and sex steroids dysregulation in PCOS group was evaluated and compared to controls of Non-obese healthy women.MethodsFF of 50 non-obese healthy women and 50 women with PCOS (18-36 years old) who were candidates for IVF/ICSI was aspirated on the oocyte retrieval day. Sex steroids and 25(OH)D levels were measured by ELISA. Reactive oxygen species (ROS) levels, total antioxidant capacity (TAC), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were assessed by chemiluminescence and spectrophotometric methods. Data were analyzed by unpaired t-test or Mann-Whitney test, and Pearson correlation coefficient. The p<0.05 was considered statistically significant.ResultsEstradiol, progesterone, 25(OH)D, TAC, and activities of SOD, GPx, and CAT in FF of women with PCOS were significantly lower, whilst their free and total testosterone and ROS levels were significantly higher than controls. There were significant positive correlations between FF levels of 25(OH)D with TAC, estradiol and progesterone concentrations, SOD, GPx, and CAT activities. Negative correlations were found between 25(OH)D with free and total testosterone, and ROS levels.ConclusionDespite different hormonal and antioxidant levels in FF of normal and cystic follicles, the correlation between 25(OH)D levels with sex steroids and oxidative stress markers showed a possible role of 25(OH)D in regulating sex hormones secretion and enhancement of antioxidant defense.Keywords: Oxidative stress, Polycystic ovarian syndrome, Sex steroid hormones, Vitamin D
Pages 143-150BackgroundThe purpose of the study was to evaluate the role of clinical, metabolic, hormonal and ultrasound features of women with PCOS in predicting the response to clomiphene citrate in treatment of infertility.MethodsA prospective observational study was done over a period of one year. A total of 164 women with PCOS related infertility were enrolled. They were treated with an incremental dose of clomiphene citrate starting with 50 mg/day to a maximum of 150 mg over 3 cycles. The response was recorded as either presence or absence of ovulation. Multiple logistic regression was used to analyze various clinical, metabolic, hormonal and ultrasound features in these women. Sensitivity and specificity of each of these parameters in predicting non-responsiveness (failure to ovulate with 150 mg clomiphene) were calculated.ResultsFerriman-Gallwey score, androstenedione levels, HDL, and cholesterol were found to be the independent predictors of non-responsiveness to clomiphene citrate. The overall best predictor of non-responsiveness to clomiphene citrate is Ferriman- Gallwey score (FG). FG score, with a cut off value of 15, had 73.9% sensitivity and 86.8% specificity in predicting non-responsiveness to clomiphene. BMI was the best anthropometric predictor of the non-responsiveness to clomiphene. Fasting insulin was the best metabolic predictor of the non-responsiveness to clomiphene. AFC was the best ovarian reserve marker as the predictor of the non-responsiveness to clomiphene (cut-off value of 11.75 with 73.9% sensitivity and 73.7% specificity).ConclusionFerriman-Gallwey score, androstenedione levels, and lipid profile are clinically useful parameters to predict which groups of PCOS women are unlikely to respond to clomiphene.Keywords: Anti- mullerian hormone, Body Mass Index, Clomiphene, Hyperandrogenism, Polycystic ovarian syndrome
Pages 151-160BackgroundUterine leiomyomas are steroid hormone dependent myometrial neoplasms of female genital tract which appear after menarche and regress at menopause. The present study evaluated the role of ER-β gene polymorphisms (rs3020449 C/T, rs3020450 G/A, rs1271572 G/T, rs1256049 G/Aand rs4986938 G/A) in the etiology of disease.MethodsA total of 150 clinically, ultrasonographically evaluated uterine leiomyoma patients and an equal number of individuals as controls were considered for the present study. Genotype analysis was carried out by TETRA Primer Amplification Refractory Mutation System–PCR for promoter polymorphisms and PCR- RFLP method was done for exonic polymorphisms followed by agarose gel electrophoresis. The strength of the association of ER-β gene polymorphisms between controls and patients were measured by appropriate statistical methods.ResultsAn increased frequency of T/T genotype and T allele of rs3020449, AA genotype and A allele of rs3020450, T/T genotype and T allele of rs1271572, AA genotype and A allele of rs1256049 and A/A genotype and A allele of rs4986938 was observed in cases when compared with controls.ConclusionThe study indicates that the ER-β gene polymorphisms may act as a major genetic regulator in the etiology of uterine leiomyomas.Keywords: Cell proliferation, Estrogens, Leiomyoma, Myometrium, Neoplasms, Transcription factors, Uterus
Pages 161-168BackgroundThere are limited data on the role of nutrient patterns in development of polycystic ovary syndrome (PCOS). The aim of the study is to document the relationship between nutrient patterns and PCOS.MethodsIn this study, 281 incident PCOS women and 472 controls were interviewed through the endocrine clinics between February 2013 and March 2015 in Tehran, Iran. Usual dietary intakes were obtained using a validated semi-quantitative food frequency questionnaire. Factor analysis was conducted on the basis of 32 nutrients. Unconditional logistic regression was performed to ascertain odds ratios. The p<0.05 was considered for significance level.ResultsIn principal component analysis two nutrient patterns emerged. Factor 1 had high loadings for riboflavin, niacin, pyridoxine, thiamin, magnesium, pantothenic acid, cobalamin, vitamin C, folate, vitamin D, total fiber, selenium, phosphorus, vitamin E, manganese, vitamin K, monounsaturated fatty acids, polyunsaturated fatty acids, potassium and vegetable protein. Factor 2 characterized by high loadings for carbohydrate, animal protein, fat, cholesterol, saturated fatty acid, sodium, biotin, copper, iron, fluoride, zinc, and calcium. After adjusting for potential confounders, the risk of PCOS was significantly higher in the highest tertile of factor 2 (OR: 2.38, 95% CI: 1.69-3.21). Conversely, being in the highest tertile of factor 1 was associated with a lower risk of PCOS (OR: 0.48, 95% CI: 0.21-0.82).ConclusionOur results provide a possible new insight into the interactions between nutrient intakes and PCOS.Keywords: Macronutrients, Micronutrients, Nutrient patterns, Polycystic ovarian syndrome, Principal component analysis
Effects of Group Counseling on Stress and Gender-Role Attitudes in Infertile Women: A Clinical TrialPages 169-177BackgroundInfertility stress can have a devastating impact on the lives of couples and influence their physical and psychological health. The purpose of this study was to investigate the effects of group counseling on female stress and gender-role attitudes in infertile women.MethodsThe present study is a randomized clinical trial conducted on 90 infertile women referred to Rooyesh Infertility Treatment Center in the city of Karaj, Iran. The convenience sampling method was used. Samples were divided into intervention and control groups through four-block random allocations. Accordingly, the intervention group received five-session group counselling and the control group only received routine care. Newton’s fertility problem inventory (FPI) and gender role questionnaire (GRQ) were used for collecting data before, after, and one month after the intervention. The significance level was set at 0.05.ResultsThe result showed a significant relationship between gender role attitude and stress in infertile women (p=0.03) and indirect association between of them (r=0.13). And also repeated measures test indicated that length of time had affected the total scores of infertility stress (p<0.001) and gender role attitude scores (p=0.001) and there was a significant difference between the two groups in infertility stress scores (p<0.001) and gender role attitude scores (p=0.001).DiscussionGroup counseling can be used in stress reduction and also improved gender role attitude of infertile women.Keywords: Counseling, Gender role, Infertility, Stress
Pages 178-190BackgroundInfertility is considered an important phenomenon in couples’ life. Infertility and its treatment process influence all aspects of the individual’s life. This study aimed to explain the psycho-social process of social construction of infertility among Iranian infertile women.MethodsThis was a qualitative study using a grounded theory approach. The study setting was the Vali-e-Asr Fertility Health Research Center and Avicenna Fertility clinic in Tehran. The sampling started purposefully and it was continued theoretically. The data collection was performed by using 36 semi-structured interviews, observation and field notes with 27 women who suffered from primary and secondary infertility having no living child. The method suggested by Strauss and Corbin was used for data analysis.ResultsResults indicate that "Concerns over life instability" and "being judged by others" were the participants’ most important preoccupation. Attempts to stabilize life and get rid of being judged by others were key aspects of the social construction of infertility and the main strategies for resolving their preoccupation. This core concept explained the basic psychological-social process of infertility in relation to axial codes.ConclusionThe results of the study show that various interactive factors affect the social construction of infertility among infertile women who focus on the central concept of attempts to stabilize life and get rid of being judged by others. Therefore, in order to achieve this goal, infertile women should be empowered by effective coping strategies.Keywords: Grounded theory, Infertile women, Infertility, Social construction
Patient with Disorders of Sex Development (DSD): A Case Report from a Tertiary Care Hospital in Thiruvananthapuram, IndiaPages 191-194Background46 XX male syndrome, a rare case of infertility was first reported by de la Chapelle in 1964. In newborn males, the incidence rate of the syndrome varies from 1/9000 to 1/20000. Here, a case of 46 XX male syndrome is reported with clinical, biochemical and genetic changes of the patient and normal masculine features.Case PresentationA 29 year old male with infertility registered at the Sree Avittom Thirunal Hospital of Government Medical College, Thiruvananthapuram for fertility treatment. He was diagnosed with non obstructive azoospermia in repeated semen analysis. Chromosomal analysis on peripheral blood lymphocytes has revealed 46 XX male syndrome and the result was confirmed with Fluorescent In situ Hybridization (FISH). Real time polymerase chain reaction failed to detect genes on azoospermia factor regions, AZFa, AZFb and AZFc of Y chromosome, but detected SRY gene positivity. Masculine features of patient were normal except small sized testis, ejaculatory dysfunction and azoospermia.ConclusionAppearance of the external genitalia will be generally normal in 46 XX with SRY positive males and generally difficult to identify before puberty because there will not be any significant clinical indication. The present case report demonstrates that mere physical or clinical examination may not disclose the genetic defects. Therefore, in addition to general examination, it is essential to perform genetic analysis on men with infertility.Keywords: 46 XX male syndrome, Azoospermia, SRY gene, Y chromosome microdeletion
Pages 195-197It is widely known that mercury (Hg) is highly toxic to humans. Environmental Hg pollution still represents a huge health concern worldwide (1). Human industrial activities have led to raised levels of Hg in the air, soil, and fresh and sea waters, and to bioaccumulation along the food chain. Humans easily absorb Hg through fish consumption. Also, it is a major toxicant because it has adverse effects on human reproductive health (2). Mercury, particularly in its organic forms, methyl-Hg and ethyl-Hg, is toxic even when individuals are exposed to relatively low Hg levels (3). Toxic effects of Hg can easily be observed in the nervous, digestive, and immune systems, in addition to lungs, kidneys, skin, and eyes, as reported by the World Health Organization (4). Many of these effects are mediated by the host’s immune response via its limited detoxification and metal excretion capabilities. Genetic polymorphism of scavenging Hg-complexed proteins are factors that can induce stressor effects, which also depend on the capability of enzymatic detoxification systems, aside from the dose of the toxicant (5).
The evidence that organic Hg easily crosses the placental barrier and reaches the fetus represents another great concern. Thereby, Hg is a major cause of neural developmental defects including delayed postnatal development (6). Both elemental Hg0 and methyl-Hg easily cross the placenta, and it should be emphasized that the developing fetal brain is the most sensitive organ. However, the more recent debate about the toxicity of dietary Hg in fetal or prenatal toxicology (7) has revealed controversies about Hg effects on fetal development, particularly because it is difficult to establish a reliable Hg-pharmacokinetics in adult women undergoing pregnancy. The pharmacokinetics and threshold of plasma Hg-acceptable levels in pregnancy are still matters of debate, and updated evidence-based official guidelines are generally lacking (8).
Recent reports together with the previous information from the Minimata and Iraq disasters have reignited this debate (9). Mercury exposure may explain cases of idiopathic infertility in males as well as in females (10). Moreover, it affects chromosomes or embryonic cell DNA, presumably by its interference with one-carbon transfer since a methionine carrier transports it across membranes (11). Recent evidence has reported that Hg inhibits the energy metabolism of spermatozoa, thus preventing their normal functioning (12). Methyl-Hg causes reproductive organ damage in women (13).
Furthermore, menstrual disorders, sterility, and spontaneous abortion following abnormal Hg toxicology have been reported (14). Spontaneous abortion can occur when the pregnant woman is exposed to organic Hg or other toxic agents (15). Many spontaneous abortions do not have a known cause, but reports indicate that Hg exposure might be a triggering factor in several cases (16). Paternal exposure to Hg, and to other industrial chemicals, and pesticides are also presumed to play a role 17). Studies on a Chinese population revealed that neural tube defects were associated with exposure to methyl-Hg in pregnancy and higher placental deposition of the compound (18). Based on the current knowledge, great concerns have been raised regarding Romanian districts with remarkably high Hg pollution (19).
Regarding pre-and postnatal risks of Hg exposure, it is relevant that the concentrations of Hg in the nervous system and other target organs of children may be higher than in the mothers, in part due to the small weight of a newborn child associated with a high rate of gastrointestinal absorption and low renal excretion, implying that hazardous Hg exposure may continue after birth (20).
Taken together, the comments presented here illustrate that the relationship between Hg toxicology and fertility has still been scarcely addressed in the literature, despite previous lessons from Minimata and some few reports in recent years. Apparently, Hg exposure may have a considerable impact on multiple stages of reproduction, from before conception to the maturation of organs and endocrine systems and further to the healthy development of the child. Therefore, a continued systematic investigation and assessment of the current state of knowledge about congenital and developmental anomalies with possible associations to environmental pollutants are of particular importance.