Medical Research

Family planning in India: The way forward Poonam Muttreja, Sanghamitra Singh Indian Journal of Medical Research 2018 148(7):1-9 Given the magnitude of the family planning programme in India, there is a need to strengthen the coordination of all its aspects, focusing on planning, programmes, monitoring, training and procurement. The quality of care in family planning must be a major focus area to ensure the success of family planning programmes. Despite serious efforts and progress, India has yet to achieve its family planning goals. Furthermore, there is a need for greater male participation both as enablers and beneficiaries and also address the sexual and reproductive needs of the youth. It is imperative for the government to ensure the prioritization of family planning in the national development agenda. Family planning is crucial for the achievement of the sustainable development goals, and subsequent efforts need to be made to improve access and strengthen quality of family planning services.

Infertility & assisted reproduction: A historical & modern scientific perspective Radhey Shyam Sharma, Richa Saxena, Rajeev Singh Indian Journal of Medical Research 2018 148(7):10-14 Infertility has always been considered as a social stigma and has often been treated as socially, mentally and physically damaging experience for the childless women rather than man. Fatherhood was more a social rather than biological concept, thereby making childlessness a legitimate ground for divorce and a matter of disgrace for women. Every country has its own set of customs and traditional beliefs for the relief of childlessness. While introducing a second wife was one way to overcome the predicament of childlessness, divorce was also an available choice. There were several myths that contemplated the human concerns and their needs during ancient times. It is evident that types of the infertility and their treatment in the modern era have some historical background and different representations in the ancient civilizations. The present review discusses the historical and modern perspectives of infertility and assisted reproduction and their importance in different cultures.

Mid-life fertility: Challenges & policy planning Umesh N Jindal Indian Journal of Medical Research 2018 148(7):15-26 This review highlights the challenges, priority areas of research and planning, strategies for regulation of services and the need to develop guidelines and laws for fertility treatments during mid-life. The success rate of all treatments is poor in advanced age women because of declining ovarian reserve and natural fertility. There is often a need of third-party involvement which has its own ethical, legal and medical issues. Welfare of children born to older women and early death of parents are important concerns. Most of the new techniques such as the pre-implantation genetic diagnosis, oocyte augmentation, use of stem cells or artificial gametes, ovarian tissue preservation and ovarian transplantation are directed to improve, preserve or replace the declining ovarian reserve. These techniques are costly and have limited availability, safety and efficacy data. Continued research and policies are required to keep pace with these techniques. The other important issues include the patients' personal autonomy and right of self-determination, welfare of offspring, public vs. private funding for research and development of new technologies vs. indiscriminate use of unproven technology. It is important that mid-life fertility is recognized as a distinct area of human reproduction requiring special considerations.

Socio-economic correlates of bereavement among women - Examining the differentials on social axes Sanghmitra S Acharya Indian Journal of Medical Research 2018 148(7):27-37 Death, disease and disaster can inflict anyone, anywhere and at any time. While occurrence of such an event could be absolved of any selective strike, the outcome reflects otherwise. Historical deprivations experienced by certain populations have caused more bereavement and sorrow to them than those who have experienced lesser or no deprivation. Therefore, the process which shapes the factors to yield such a result is important and needs to be understood for any policy suggestions and programmatic inputs. Loss of pregnancy and newborn inflicts sorrow and bereavement across space, time and social labyrinth. The degree of bereavement is likely to reduce with time, but space and social context govern the response to it. Therefore, factors contributing to the differentials vary in their demographic, social and economic characteristics. The loss of pregnancy and newborn remains inadequately addressed. Family and community play a significant role in coping. While the developed countries have institutional structure to address coping with the loss, the South Asian countries rely heavily on the family and the community for such support. The present review examines these trajectories across social groups.

Stem cells survive oncotherapy & can regenerate non-functional gonads: A paradigm shift for oncofertility Deepa Bhartiya Indian Journal of Medical Research 2018 148(7):38-49 A large proportion of patients who survive cancer are rendered infertile as an unwanted side effect of oncotherapy. Currently accepted approaches for fertility preservation involve banking eggs/sperm/embryos or ovarian/testicular tissue before oncotherapy for future use. Such approaches are invasive, expensive, technically challenging and depend on assisted reproductive technologies (ART). Establishing a gonadal tissue bank (for cancer patients) is also fraught with ethical, legal and safety issues. Most importantly, patients who find it difficult to meet expenses towards cancer treatment will find it difficult to meet expenses towards gonadal tissue banking and ART to achieve parenthood later on. In this review an alternative strategy to regenerate non-functional gonads in cancer survivors by targeting endogenous stem cells that survive oncotherapy is discussed. A novel population of pluripotent stem cells termed very small embryonic-like stem cells (VSELs), developmentally equivalent to late migratory primordial germ cells, exists in adult gonads and survives oncotherapy due to their quiescent nature. However, the stem-cell niche gets compromised by oncotherapy. Transplanting niche cells (Sertoli or mesenchymal cells) can regenerate the non-functional gonads. This approach is safe, has resulted in the birth of fertile offspring in mice and could restore gonadal function early in life to support proper growth and later serve as a source of gametes. This newly emerging understanding on stem cells biology can obviate the need to bank gonadal tissue and fertility may also be restored in existing cancer survivors who were earlier deprived of gonadal tissue banking before oncotherapy.

Dendritic cell engineering for selective targeting of female reproductive tract cancers Arpit Bhargava, Rupesh Kumar Srivastava, Dinesh Kumar Mishra, Rajnarayan R Tiwari, Radhey Shyam Sharma, Pradyumna Kumar Mishra Indian Journal of Medical Research 2018 148(7):50-63 Female reproductive tract cancers (FRCs) are considered as one of the most frequently occurring malignancies and a foremost cause of death among women. The late-stage diagnosis and limited clinical effectiveness of currently available mainstay therapies, primarily due to the developed drug resistance properties of tumour cells, further increase disease severity. In the past decade, dendritic cell (DC)-based immunotherapy has shown remarkable success and appeared as a feasible therapeutic alternative to treat several malignancies, including FRCs. Importantly, the clinical efficacy of this therapy is shown to be restricted by the established immunosuppressive tumour microenvironment. However, combining nanoengineered approaches can significantly assist DCs to overcome this tumour-induced immune tolerance. The prolonged release of nanoencapsulated tumour antigens helps improve the ability of DC-based therapeutics to selectively target and remove residual tumour cells. Incorporation of surface ligands and co-adjuvants may further aid DC targeting (in vivo) to overcome the issues associated with the short DC lifespan, immunosuppression and imprecise uptake. We herein briefly discuss the necessity and progress of DC-based therapeutics in FRCs. The review also sheds lights on the future challenges to design and develop clinically effective nanoparticles-DC combinations that can induce efficient anti-tumour immune responses and prolong patients' survival.

Postpartum uterine infection & ovarian dysfunction Sunita Dahiya, Suman Kumari, Payal Rani, Suneel Kumar Onteru, Dheer Singh Indian Journal of Medical Research 2018 148(7):64-70 Postpartum uterine infections such as metritis, endometritis and mastitis have been considered as underlying causes for ovarian dysfunction in mammals. Almost all mammals, particularly dairy animals are susceptible to postpartum uterine infections, resulting in impaired fertility and economic loss. One of the factors for low fertility in females is ovarian dysfunction, which is exhibited as impaired growth and function of ovarian follicles by the postpartum infection. Immune system of mammals provides a host defence mechanism against pathogenic microbes through the recognition of pathogen-associated molecular patterns (PAMPs) and forming inflammasomes. Like immune cells, ovarian granulosa cells also exhibit a similar pattern of cytokine gene expressions on exposure to PAMPs. Genome-wide transcriptomic approaches explored the molecular mechanisms underlying the immune function of buffalo granulosa cells during endotoxin exposure. Understanding the molecular mechanism of ovarian dysfunction due to uterine infection would be helpful to implement various strategies to handle the adverse effects of postpartum uterine disease on fertility by developing potential therapeutics. Therefore, this article focuses on key factors that are responsible for postpartum infection and particularly summarizes the molecular mechanism of infection underlying the ovarian dysfunction in dairy animals.

Female genital tuberculosis: Revisited Jai Bhagwan Sharma, Eshani Sharma, Sangeeta Sharma, Sona Dharmendra Indian Journal of Medical Research 2018 148(7):71-83 Female genital tuberculosis (FGTB) is caused by Mycobacterium tuberculosis (rarely Mycobacterium bovis and/or atypical mycobacteria) being usually secondary to TB of the lungs or other organs with infection reaching through haematogenous, lymphatic route or direct spread from abdominal TB. In FGTB, fallopian tubes are affected in 90 per cent women, whereas uterine endometrium is affected in 70 per cent and ovaries in about 25 per cent women. It causes menstrual dysfunction and infertility through the damage of genital organs. Some cases may be asymptomatic. Diagnosis is often made from proper history taking, meticulous clinical examination and judicious use of investigations, especially endometrial aspirate (or biopsy) and endoscopy. Treatment is through multi-drug antitubercular treatment for adequate time period (rifampicin, isoniazid, pyrazinamide, ethambutol daily for 60 days followed by rifampicin, isoniazid, ethambutol daily for 120 days). Treatment is given for 18-24 months using the second-line drugs for drug-resistant (DR) cases. With the advent of increased access to rapid diagnostics and newer drugs, the management protocol is moving towards achieving universal drug sensitivity testing and treatment with injection-free regimens containing newer drugs, especially for new and previously treated DR cases.

Redox regulation & sperm function: A proteomic insight Gayatri Mohanty, Luna Samanta Indian Journal of Medical Research 2018 148(7):84-91 Infertility affects nearly 15 per cent of all couples within the reproductive age worldwide, with about 50 per cent being exhibited in the male, called male factor infertility. Successful reproduction is dependent on sperm chromatin integrity. Spermatozoa are highly specialized cells that aim to transmit the paternal genomic blueprint to the oocyte. The spermatozoon is regulated by redox mechanisms during its epididymal transit to acquire fertilizing ability. While, at physiological levels, the production of reactive oxygen species (ROS) supports the spermatozoon to acquire its fertilizing ability, at high concentrations, it affects sperm function leading to infertility. Emerging proteomic technologies provide an opportunity to address these key issues that may solve many fertility-associated problems resulting from oxidative stress (OS). This review highlights the need for an efficient therapeutic approach to male infertility with the application of high-throughput OS-mediated proteomic technology, and also addresses the question as to whether targeting these altered sperm-specific proteins may help in designing an efficient and reversible male contraceptive.

Effect of radiofrequency radiation on reproductive health Rajeev Singh, Ravindra Nath, Ajit Kumar Mathur, Radhey Shyam Sharma Indian Journal of Medical Research 2018 148(7):92-99 The development of cellular phone system has greatly increased the extent and magnitude of radiofrequency radiation (RFR) exposure. The RFR emitted from mobile phone and mobile phone base stations exerts thermal and non-thermal effects. The short-term and long-term exposure to RFR may have adverse effect on humans as well as animals. Most laboratory studies have indicated a direct link between exposure to RFR and adverse biological effects. Several in vitro studies have reported that RFR induces various types of cancer and DNA or chromosomal damage. On the other hand, some animal studies have not reported adverse effects of this radiation. The present review summarizes information available on the possible effects of RFR on the reproductive health.