Year : 2019 | Volume
: 12 | Issue : 1 | Page : 1--3
From the editor's desk
Dr. Patil's Fertility and Endoscopy Clinic, Bengaluru, Karnataka, India
Dr. Madhuri Patil
Dr. Patil's Fertility and Endoscopy Clinic, Bengaluru, Karnataka
|How to cite this article:|
Patil M. From the editor's desk.J Hum Reprod Sci 2019;12:1-3
|How to cite this URL:|
Patil M. From the editor's desk. J Hum Reprod Sci [serial online] 2019 [cited 2019 Jul 17 ];12:1-3
Available from: http://www.jhrsonline.org/text.asp?2019/12/1/1/255782
This issue has two review articles on male subfertility. One is on the role of oxidative stress (OS) in male infertility and other on the proteins as molecular markers of male infertility. We know that sperm is a very sophisticated toolbox, an optimally elected cell with high-quality DNA, centrosome, RNA species, histone code, and as yet several unknown factors that could influence fertilization. There are several factors such as accessory gland infection, lifestyle, endocrine disorders (diabetes), varicocele, and presence of immature sperms and dysfunctional sperms that contribute to OS-induced male infertility. OS results in the generation of reactive oxygen species (ROS), which has a negative correlation with sperm concentration, motility, morphology, and overall normal semen parameters and can also damage DNA. Thus, “OS contributes to defective spermatogenesis and sperm function, leading to male factor infertility.” Despite this, the evaluation of ROS is not a mainstream investigation in male infertility as the standardization of testing and the availability of these tests remain limited. There is also lack of a well-defined therapeutic strategy for OS, and the most important point one has to remember is that small amounts of ROS are necessary for spermatozoa to acquire fertilizing abilities (capacitation, acrosome reaction, hyperactivation, motility, and sperm-oocyte fusion). Thus, till date, there is no consensus on whether and which laboratory test should be done for testing ROS and which antioxidant should be used and for how long. Further large randomized controlled trials (RCTs) are necessary before we arrive at a consensus.
Several molecular markers can be proposed for male fertility. However, whether the markers can specifically identify defects in the fertilizing ability of human sperm awaits further studies. Of these several markers, proteins play a key role in many functions of the sperm. Identification of such proteins in the seminal plasma could provide better insights into the physiological processes and the nature of subfertility or infertility. The review article in this issue discusses the role of evaluation of several proteins in the seminal plasma and their role in varied sperm functions and whether testing for these proteins could give us a better understanding of the fertility potential of the sperm instead of parameters such as motility and morphology which are routinely evaluated.
There is an original article that looks at the role of antioxidant enzyme glutathione S-transferases (GSTs) in the defense mechanism of sperm cells in fertile and infertile men. This study concluded that sperm GSTs are important in the defense mechanism against OS and its evaluation in infertile men can serve as an important test for the evaluation of treatment using antioxidants.
We have another retrospective study of 18 years on karyotyping of patients with primary amenorrhea. Primary amenorrhea is usually the result of a genetic or anatomical abnormality but may also be due to hypothalamic disorders, such as hypogonadotropic hypogonadism, due to abnormal secretion or inhibition of gonadotropin-releasing hormone or autoimmune conditions and iatrogenic causes related to surgery, chemotherapy, and radiotherapy. Genetic causes include Turner's syndrome (46XO) and Swyer syndrome (46XY), whereas single-gene disorders include fragile X premutation (FMR1 premutation) and deficiencies in the steroidogenic pathway enzymes. Although in the literature genetic abnormality accounts for maximum etiological cause for primary amenorrhea, this study has reported an incidence for chromosomal abnormalities as a cause only in 13.22% of the 174 cases analyzed.
Tuberculosis (TB) is still endemic in several areas in India but probably over diagnosed and over treated in the infertile population. The methods available for the detection of TB include acid-fast bacilli (AFB) smear microscopy, histopathology, culture, and polymerase chain reaction (PCR) (DNA or RNA). Unfortunately, today, DNA-PCR is being done rampantly and several women are being subjected to anti-TB treatment, which has increased the incidence of drug resistance. This is because DNA-PCR can yield positive result even in the presence of single dead bacillus, and thus, the trend should shift toward doing RNA PCR which detects only live bacilli or culture and histopathology. The index guidelines on extrapulmonary TB for India were published in March 2016, which states that the diagnosis of female genital TB (FGTB) should be made based on laparoscopic appearance typical for FGTB, any gynecological specimen being positive for AFBs on microscopy or positive for Mycobacterium tuberculosis on culture and histopathological examination. They have also suggested the use of fluorodeoxyglucose positron emission tomography-computed tomography in selected cases. There is no mention of either RNA or DNA PCR anywhere, but most evaluations of FGTB are being done by these methods. Despite this, there are several papers published on molecular diagnosis of TB by PCR and have shown to have great potential to improve the ability of diagnosis of FGTB. However, there are many who propose both culture and PCR for diagnosis of GTB to avoid any kind of false-negative result occurred during different steps of diagnosis. In the study by Lavina Chaubey from Uttar Pradesh who compared the results of nested PCR for early diagnosis of FGTB using menstrual blood and endometrial tissue from infertile female population concluded that nested PCR in the menstrual blood seems to be a good option for early diagnosis of FGTB. In my view, before we use these techniques as a universal screening technique, one must validate it in large RCTs.
There is another study on OS and its correlation with severity of endometriosis. ROS are generated in endometriotic tissues that can have adverse impacts on oocyte, sperm, and embryos, thus compromising the success rate of any infertility treatment. This is because ROS are inflammatory mediators known to modulate cell proliferation and to have deleterious effects. There are also studies that demonstrate a key role for ROS in the growth and/or maintenance of endometriotic lesions. OS is seen when the balance between ROS production and antioxidant defense is disrupted, which may be due to either inadequate antioxidant protection or excess production of ROS. The aim of the study published from Kasturba Medical College, Manipal, was to evaluate the association between OS in the blood and peritoneal fluid and severity of endometriosis. It demonstrated that OS is present in all women with endometriosis and increases with severity of the disease. Identification and evaluation of these OS markers may open the way to the evaluation of therapeutic approaches in treating endometriosis. Identification of these markers may also serve as noninvasive diagnostic markers, which if identified and treated will prevent progression of endometriosis. Clinical trials need to be conducted to identify the use of antioxidants as potential therapies for endometriosis.
Infertility can be one of the most stressful and life-changing events a person can face. Emotional distress in infertility treatment, especially in vitro fertilization (IVF), is as high as 38% and is mainly due to relational strain in between the couple due to infertility, fear, and negative attitudes to treatment and psychological vulnerability and ability to withstand demands of treatment. Unsuccessful treatment provokes grief and mourning whereas successful treatment decreases the emotional distress. It has also been noted that women are usually more emotionally affected compared to their male partners. This stress then can affect their social and sexual life and interpersonal relationship. However, infertility counseling is mandatory and is an integral component of infertility treatment at the first visit to giving basic information concerning individual treatment and the emotional implications, which helps patients to integrate the process. Screening instruments are helpful for identifying patients with treatment-related stress and should be used in all couples so as to identify couples requiring psychotherapy. The study on anxiety and stress at different stages of IVF treatment by Manisha Awtani et al. concluded that both anxiety and stress are present throughout treatment and the waiting period till confirmation of pregnancy was the most anxious period. Therefore, psychological counseling should be offered to all infertile couples independent of their individual diagnosis or the stage of medical treatment and independent of treatment.
In a multicenter study, a new indigenous recombinant human chorionic gonadotropin (r-hCG) developed in India was compared for efficacy and safety with Ovitrelle, an r-hCG from Merck Serono in intrauterine insemination (IUI) cycles. The primary outcome compared was ovulation rate, while the secondary outcomes looked at were pregnancy rates, incidence of adverse events, and development of immunogenicity. The ovulation and biochemical pregnancy rate were comparable in the two groups. The incidents of adverse events either mild or moderate reported were higher in the indigenous group.
After 40 years of IVF treatment and research, major progress has been made in improving stimulation protocols and fertilization procedures, optimizing embryo culture conditions, and preventing premature luteinization. However, only marginal improvement is seen in the implantation and pregnancy rates. One of the major factors which affect the implantation and pregnancy rate is endometrial receptivity. One of the test developed is endometrial receptivity array (ERA), which can determine the endometrial receptivity by the identification of the transcriptomic signature composed by the expression of 238 genes.
The profile differences are implemented in a computational predictor that can diagnose objectively the personalized window of implantation (WOI). ERA can diagnose abnormalities in the endometrial response (presence of sufficient progesterone and appropriate timing) and is reproducible in subsequent cycles. Thus, identifying the WOI displacements in women with recurrent implantation failure, one can perform personalized embryo transfer (ET) to treat problems of endometrial receptivity that may be the result of individual physiological variation and optimize the ART outcome. The study by Jayesh A. Patel compared the implantation, pregnancy, and ongoing pregnancy rate in patients with receptive ERA who underwent a routine ET and those with nonreceptive ERA who underwent a personalized ET and found it to be comparable.
There is a case series published on the investigations, psychosocial impact, and management of vaginal agenesis. Müllerian agenesis is the second most common cause of primary amenorrhea, and this includes Mayer–Rokitansky–Küster–Hauser syndrome and vaginal agenesis or presence of transverse septum. Vaginal dilation therapy is still widely considered the first-line treatment because success rates are high and associated risks are low. A variety of surgical options are also available although long-term outcome studies on most surgical techniques are still lacking. Moreover, the medical literature lacks prospective comparative outcome studies, between surgical and nonsurgical techniques. The study published in this issue looks at the importance of counseling on the postoperative outcome in terms of psychological and sexual satisfaction of the couple and treatment of primary amenorrhea and infertility.
There is a case report on balanced reciprocal translocation as a cause of infertility in the female.