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   2014| November  | Volume 140 | Issue 7  
    Online since February 10, 2015

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Social, ethical, medical & legal aspects of surrogacy: an Indian scenario
RS Sharma
November 2014, 140(7):13-16
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Association of western diet & lifestyle with decreased fertility
P Nazni
November 2014, 140(7):78-81
It has been accepted that food customs are closely associated with the quality of life in both men and women's reproductive life. Food customs are speculated to not only influence the present lifestyle but also to induce gynaecological disorders such as dysmenorrhoea, spermatogenesis and irregular menstruation. Though there is no consistent definition of regular or normal menstruation, epidemiologic evaluation of menstrual cycle has been becoming an important issue. In addition, latent development of organic diseases such as endometriosis, which are accompanied by dysmenorrhoea, is a concern under the current nutritional environment. Thus, it is an important issue to evaluate the present situation of eating habits in couples and estimate the influence of these habits on the quality of reproductive functions. A multi-faceted therapeutic approach to improving fertility involves identifying harmful environmental and occupational risk factors, while correcting underlying nutritional imbalances to encourage optimal reproduction and its function.
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RISUG: An intravasal injectable male contraceptive
NK Lohiya, I Alam, M Hussain, SR Khan, AS Ansari
November 2014, 140(7):63-72
Over the last two decades RISUG has been drawing attention in the field of male contraception. It promises to sterile men for a period of up to 10-15 years. According to recent studies in animal models, it proves to be completely reversible. Practically, there are no better options available that can assure complete sterility and precise reversibility. Regardless of so much of information available, RISUG is still holding up for many reasons, firstly, the available information engender bewilderment such as what is this copolymer, how does it work and is reversal really possible? Secondly, advancement of this outstanding invention is drastically slow and thirdly, effects of long-term contraception with RISUG and reports on evaluation of anomalies (if any) in F 1 , F 2 progenies, are lacking. In this review the lacunae as well as advances in the development of RISUG in the light of published work and available resources are pointed out. Formulation of the RISUG, its mode of action and clinical trials have been addressed with particular emphasis.
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Emergency contraception - Potential for women's health
Suneeta Mittal
November 2014, 140(7):45-52
Emergency contraception (EC) is a safe and effective method which is used to prevent unwanted pregnancy after unprotected sexual intercourse. Many of the unwanted pregnancies end in unsafe abortions. The search for an ideal contraceptive, which does not interfere with spontaneity or pleasure of the sexual act, yet effectively controls the fertility, is still continuing. Numerous contraceptive techniques are available, yet contraceptive coverage continues to be poor in India. Thus, even when not planning for a pregnancy, exposure to unprotected sex takes place often, necessitating the use of emergency contraception. This need may also arise due to failure of contraceptive method being used (condom rupture, diaphragm slippage, forgotten oral pills) or following sexual assault. Emergency contraception is an intervention that can prevent a large number of unwanted pregnancies resulting from failure of regular contraception or unplanned sexual activity, which in turn helps in reducing the maternal mortality and morbidity due to unsafe abortions. However, a concern has been expressed regarding repeated and indiscriminate usage of e-pill, currently the rational use of emergency contraception is being promoted as it is expected to make a significant dent in reducing the number of unwanted pregnancies and unsafe abortions. In fact, since the introduction of emergency contraception, the contribution of unsafe abortion towards maternal mortality has declined from 13 to 8 per cent.
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Biological control of vaginosis to improve reproductive health
P Mastromarino, R Hemalatha, A Barbonetti, B Cinque, MG Cifone, F Tammaro, F Francavilla
November 2014, 140(7):91-97
The human vaginal microbiota plays an important role in the maintenance of a woman's health, as well as of her partner's and newborns'. When this predominantly Lactobacillus community is disrupted, decreased in abundance and replaced by different anaerobes, bacterial vaginosis (BV) may occur. BV is associated with ascending infections and obstetrical complications, such as chorioamnionitis and preterm delivery, as well as with urinary tract infections and sexually transmitted infections. In BV the overgrowth of anaerobes produces noxious substances like polyamines and other compounds that trigger the release of pro-inflammatory cytokines interleukin (IL)-1 β and IL-8. BV can profoundly affect, with different mechanisms, all the phases of a woman's life in relation to reproduction, before pregnancy, during fertilization, through and at the end of pregnancy. BV can directly affect fertility, since an ascending dissemination of the involved species may lead to tubal factor infertility. Moreover, the increased risk of acquiring sexually transmitted diseases contributes to damage to reproductive health. Exogenous strains of lactobacilli have been suggested as a means of re-establishing a normal healthy vaginal flora. Carefully selected probiotic strains can eliminate BV and also exert an antiviral effect, thus reducing viral load and preventing foetal and neonatal infection. The administration of beneficial microorganisms (probiotics) can aid recovery from infection and restore and maintain a healthy vaginal ecosystem, thus improving female health also in relation to reproductive health.
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Priority strategies for India's family planning programme
Saroj Pachauri
November 2014, 140(7):137-146
Strategies to accelerate progress of India's family planning programme are discussed and the importance of improving the quality and reach of services to address unmet contraceptive need by providing method choice is emphasized. Although there is a growing demand for both limiting and spacing births, female sterilisation, is the dominant method in the national programme and use of spacing methods remains very limited. Fertility decline has been slower in the empowered action group (EAG) s0 tates which contribute about 40 per cent of population growth to the country and also depict gloomy statistics for other socio-development indicators. It is, therefore, important to intensify efforts to reduce both fertility and mortality in these s0 tates. a0 rationale has been provided for implementing integrated programmes using a gender lens because the lack of women's autonomy in reproductive decision-making, compounded by poor male involvement in sexual and reproductive health matters, is a fundamental issue yet to be addressed. The need for collaboration between scientists developing contraceptive technologies and those implementing family planning services is underscored. If contraceptive technologies are developed with an understanding of the contexts in which they will be delivered and an appreciation of end-users' needs and perspectives, they are more likely to be accepted by service providers and used by clients.
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Reproductive health with emphasis on strategies for family planning
RS Sharma
November 2014, 140(7):1-2
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Environmental & lifestyle factors in deterioration of male reproductive health
Sunil Kumar, Shiva Murarka, VV Mishra, AK Gautam
November 2014, 140(7):29-35
Background & objectives: Male reproductive function in the general population has been receiving attention in recent years due to reports of various reproductive and developmental defects, which might be associated with various lifestyle and environmental factors. This study was carried out to determine the role of various lifestyle and environmental factors in male reproduction and their possible association with declining semen quality, increased oxidative stress as well as sperm DNA damage. Methods: Semen samples were obtained from 240 male partners of the couples consulting for infertility problem. Semen analysis was carried out using WHO criteria and subjects were categorized on the basis of self reported history of lifestyle as well as environmental exposure. The oxidative and antioxidant markers; lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) as well as DNA damage by acridine orange test (AO) were determined. Results: The presence of abnormal semen parameters was significantly higher among the lifestyle and/or environmental exposed subjects as compared to the non-exposed population. Further, the levels of antioxidants were reduced and sperm DNA damage was more among the lifestyle and/or environmental exposed subjects, though the changes were not significant. Interpretation & conclusions: These findings indicated that various lifestyle factors such as tobacco smoking, chewing and alcohol use as well as exposure to toxic agents might be attributed to the risk of declining semen quality and increase in oxidative stress and sperm DNA damage.
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Acceptability of male condom: An Indian scenario
Balaiah Donta, Shahina Begum, DD Naik
November 2014, 140(7):152-156
The National Family Planning Programme of India had introduced condom as one of the family planning methods in the late1960s. Condom was promoted as a family planning method through social marketing since its inception. With the increasing prevalence and incidence of sexually transmitted infections (STIs) including HIV/AIDS, condom was also promoted as a dual method for protection against both unintended pregnancies as well as sexually transmitted infections. Despite efforts at various levels, the overall use of condom among couples in India is low. Here we present literature review of studies to understand the condom acceptability among couples in India. Specifically, the paper assesses research and programmes that have been carried out to increase the use of condom among couples; determinants of condom use; reason for not using condom; and perception versus experience of condom failure. The reported problems related to condom use included non acceptance by partner, perceived ineffectiveness, less comfort, lack of sexual satisfaction, husband's alcohol use, depression, and anxiety, and not available at that instant. The role of media in the promotion of condom use was indicated as an important way to increase awareness and use. Multiple strategies would help in acceptance of male condom.
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Effect of dietary phytoestrogens on human growth regulation: imprinting in health & disease
K Griffiths, DW Wilson, RB Singh, F De Meester
November 2014, 140(7):82-90
This group has advocated a return to the notional Palζolithic diet with fruits, vegetables, roots, leaves, seeds, phytochemical antioxidants and proteins, etc. Phytoestrogens, viz. lignans, isoflavonoids and flavonoids are weak oestrogenic constituents of such a diet and may have a considerable impact on human health and disease. The aim of this paper was to conduct a preliminary overview of about 2000 research-led studies from the 1930s to the present time reported in the literature on flavonoids/isoflavonoids/lignans and to assemble evidence for a future strictly formal literature review on the health benefits and risks of flavonoids in a variety of diseases.
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Promise(s) of using mesenchymal stem cells in reproductive disorders
Vijayalakshmi Venkatesan, Soundarya Lakshmi Madhira
November 2014, 140(7):98-105
In recent times, infertility among both man and woman has become a major concern affecting about 20 per cent of the population worldwide and has been attributed in part to several aetiological factors such as changes in lifestyle, which includes sedentary life, dietary habits, sleep anomalies, environmental pollution, etc. Assisted reproductive technologies (ART) have come to the rescue of many such couples, but presence of metabolic disorders such as obesity, diabetes with insulin resistance (IR) and its secondary complications (micro- and macro-vascular complications), become confounders to the outcome of ART. Cell therapies are arising as a new hope in the management of reproductive disorders and currently, the efficacy of mesenchymal stem cells (MSCs) harvested from the adult sources finds wide application in the management of diseases like stroke, neuropathy, nephropathy, myopathy, wounds in diabetes, etc. Given the capacity of MSCs to preferentially home to damaged tissue and modulate the cellular niche/microenvironment to augment tissue repairs and regeneration, the present review outlines the applications of MSCs in the management of infertility/reproductive disorders.
  1,565 356 -
Stress induced premature senescence : a new culprit in ovarian tumorigenesis?
Gorantla Venkata Raghuram, Pradyumna Kumar Mishra
November 2014, 140(7):120-129
Stress induced premature senescence (SIPS) is a relative extension to the concept of exogenous cellular insult. Besides persistent double strand (ds) DNA breaks and increased β-galactosidase activity, biological significance of telomeric attrition in conjunction with senescence associated secretory phenotype (SASP) has been highlighted in SIPS. To gain insight on the potential role of this unique phenomenon invoked upon environmental stress, we sequentially validated the molecular repercussions of this event in ovarian epithelial cells after exposure to methyl isocyanate, an elegant regulator of cellular biotransformation. Persistent accumulation of DNA damage response factors phospho-ATM/γ-H2AX, morphological changes with increased cell size and early yet incremental β-gal staining, imply the inception of premature senescence. Advent of SASP is attributed by prolonged secretion of pro-inflammatory cytokines along with untimely but significant G1/S cell cycle arrest. Telomeric dysfunction associated with premature senescence is indicative of early loss of TRF2 (telomeric repeat binding factor 2) protein and resultant multiple translocations. Induction of senescence-associated heterochromatic foci formation showcases the chromatin alterations in form of trimethylated H3K9me3 in conjunction with H4 hypoacetylation and altered miRNA expression. Anchorage-independent neoplastic growth observed in treated cells reaffirms the oncogenic transformation following the exposure. Collectively, we infer the possible role of SIPS, as a central phenomenon, to perturbed genomic integrity in ovarian surface epithelium, orchestrated through SASP and chromatin level alterations, a hitherto unknown molecular paradigm. Although translational utility of SIPS as a biomarker for estimating ovarian cancer risk seems evident, further investigations will be imperative to provide a tangible way for its precise validation in clinical settings.
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Uphill battle: The saga of hCG research that led to a paradigm shift
CV Rao
November 2014, 140(7):3-5
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Intrauterine devices & infection: Review of the literature
David Hubacher
November 2014, 140(7):53-57
The relationship between use of an intrauterine device (IUD) and pelvic inflammatory disease (PID) has been studied extensively over the past 50 years. Previous research has led to considerable controversy and debate. Numerous limitations in the studies make it difficult to draw any firm conclusions from the past research or to design new approaches to study the topic. The main research barriers include uncertainty of infection/diagnoses, and inappropriate comparison groups for IUD users. Natural history studies of the aetiology of disease and observational research among IUD users suggest that the risk of PID is very low. Research linking previous IUD use to the more distant endpoint of tubal infertility reveals that the risks may be even lower than the risks of PID.
  1,366 417 -
Use of traditional contraceptive methods in India & its socio-demographic determinants
Faujdar Ram, Chander Shekhar, Biswabandita Chowdhury
November 2014, 140(7):17-28
Background & objectives: The high use of traditional contraceptive methods may have health repercussions on both partners. High failure rate, lack of protection from sexually transmitted diseases are some of the examples of these repercussions. The aim of this study was to understand the level, trends, pattern, volume and socio-demographic determinants of using traditional contraceptive methods in the Indian context. Methods: Percentages, per cent distribution, cross-tabulation and multinomial logistic regression analyses were carried out. The data from the three rounds of National Family Health s0 urvey (NFHS) were used. The unit level District Level Household Survey (2007-2008) were mainly used to carry out the analysis in this paper. Marriage rates for States and Union Territories (UTs) were projected for the period of 2001-2011 to estimate the volume of traditional contraceptive users. These rates are required to get the number of eligible couples as on 2011 in the respective State/UT. Results: The latest round of the District Level Household Survey (2007-2008) revealed that 6.7 per cent currently married women were using traditional contraceptive methods in India. More than half of the currently married women (56%) have ever used these methods. In terms of socio-demographic determinants, the odds ratios of using these methods were significantly higher for women aged 35 years and above, rural, Hindu, other than Scheduled Castes/Tribes (SCs/STs), secondary and above educated, non-poor, having two plus living children, and at least one surviving son in most of the s0 tates as well as at the national level. The northeastern region showed higher odds ratios (5 times) of women using traditional contraceptive methods than the southern region. Interpretation & conclusions: A large number of currently married women have ever used the traditional contraceptive methods in India. On the basis of the findings from this study, the total size of those women who were using traditional methods and those who were having unmet need, and are required to use modern spacing methods of family planning in achieving the reproductive goals, is around 53 million. Women from a set of specific socio-demographic backgrounds are more likely to use these methods. A regional pattern has also emerged in use of tradition contraceptive methods in India.
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Advances in male hormonal contraception
Costantino Antonietta, Gava Giulia, Berra Marta, Meriggiola Maria Cristina
November 2014, 140(7):58-62
Contraception is a basic human right for its role on health, quality of life and wellbeing of the woman and of the society as a whole. Since the introduction of female hormonal contraception the responsibility of family planning has always been with women. Currently there are only a few contraceptive methods available for men, but recently, men have become more interested in supporting their partners actively. Over the last few decades different trials have been performed providing important advances in the development of a safe and effective hormonal contraceptive for men. This paper summarizes some of the most recent trials.
  1,151 364 -
Strategies for family planning going forward - Social marketing & expanding contraceptive choices package
Vivek Malhotra, Sunitha Bhat
November 2014, 140(7):6-8
  1,190 271 -
Sourcing human embryos for embryonic stem cell lines: Problems & perspectives
Rajvi H Mehta
November 2014, 140(7):106-111
The ability to successfully derive human embryonic stem cells (hESC) lines from human embryos following in vitro fertilization (IVF) opened up a plethora of potential applications of this technique. These cell lines could have been successfully used to increase our understanding of human developmental biology, transplantation medicine and the emerging science of regenerative medicine. The main source for human embryos has been 'discarded' or 'spare' fresh or frozen human embryos following IVF. It is a common practice to stimulate the ovaries of women undergoing any of the assisted reproductive technologies (ART) and retrieve multiple oocytes which subsequently lead to multiple embryos. Of these, only two or maximum of three embryos are transferred while the rest are cryopreserved as per the decision of the couple. In case a couple does not desire to 'cryopreserve' their embryos then all the embryos remaining following embryo transfer can be considered 'spare' or if a couple is no longer in need of the 'cryopreserved' embryos then these also can be considered as 'spare'. But, the question raised by the ethicists is, "what about 'slightly' over-stimulating a woman to get a few extra eggs and embryos? The decision becomes more difficult when it comes to 'discarded' embryos. As of today, the quality of the embryos is primarily assessed based on morphology and the rate of development mainly judged by single point assessment. Despite many criteria described in the literature, the quality assessment is purely subjective. The question that arises is on the decision of 'discarding' embryos. What would be the criteria for discarding embryos and the potential 'use' of ESC derived from the 'abnormal appearing' embryos? This paper discusses some of the newer methods to procure embryos for the derivation of embryonic stem cell lines which will respect the ethical concerns but still provide the source material.
  1,104 319 -
Variations in immunogenetics, human papillomavirus (HPV) infection & predisposition to cervical cancer in Indian women
Priyanka Gokhale, Shilpa Kerkar, Hemant Tongaonkar, Hemangi Chaudhari, Himangi Warke, Vinita Salvi, Jayanti Mania-Pramanik
November 2014, 140(7):36-43
Background & objectives: Human papillomavirus (HPV) is the main causative agent for cervical cancer. Variability in host immunogenetic factors is important in determining the overall cellular immune response to the HPV infection. This study was carried out to confirm the association between human leukocyte antigen (HLA) class II alleles and cervical cancer in HPV infected women. Methods: b0 oth low and high resolution methods were used to genotype HLA class II (DRB1 and DQB1) alleles in 75 women with cervical cancer (cases) and 75 HPV positive women and 100 HPV negative women with healthy cervix (controls). o0 dds ratio and 95% confidence interval were calculated. Co-occurring HLA alleles (haplotype) across cases and controls were also studied. Results: Significant association was found for HLA-DRB1*03(*13:01) and - DQB1*02(*02:01) with increased risk for cervical cancer. Also, HLA-DRB1*13(*13:01); -DQB1*06 and -DQB1*03:02 were significantly associated with decreased risk for cervical cancer. Haplotype analysis highlighted the significant association of HLA- DRB1*07:01-DQB1*02:02 and HLA DRB1*10:01-DQB1*05:01 with cervical cancer, while HLA-DRB1*14:04-DQB1*05:03 and DRB1*15:01-DQB1*06:01 conferred decreased risk for cervical cancer. Multivariate analysis highlighted the association of specific alleles with cervical cancer after adjusting for confounding factor age. Interpretation & conclusions: There were possible associations of specific HLA class II alleles either with risk of developing cervical cancer, or with its protection. Our results confirmed the assessment of DRB1*13 as a protective marker in HPV infection outcome. o0 ur study also revealed protective association of homozygous haplotype DRB1*15- DQB1*06 with cervical cancer.
  1,000 332 -
Development of antifertility vaccine using sperm specific proteins
AH Bandivdekar
November 2014, 140(7):73-77
Sperm proteins are known to be associated with normal fertilization as auto- or iso-antibodies to these proteins may cause infertility. Therefore, sperm proteins have been considered to be the potential candidate for the development of antifertility vaccine. Some of the sperm proteins proved to be promising antigens for contraceptive vaccine includes lactate dehydrogenase (LDH-C4), protein hyaluronidase (PH-20), and Eppin. Immunization with LDH-C4 reduced fertility in female baboons but not in female cynomolgus macaques. Active immunization with PH-20 resulted in 100 per cent inhibition of fertility in male guinea pigs but it induced autoimmune orchitis. Immunization with Eppin elicited high antibody titres in 78 per cent of immunized monkeys and induced infertility but the immunopathological effect of immunization was not examined. Human sperm antigen (80kDa HSA) is a sperm specific, highly immunogenic and conserved sperm protein. Active immunization with 80kDa HSA induced immunological infertility in male and female rats. Partial N-terminal amino acid sequence of 80kDa HSA (Peptide NT) and its peptides (Peptides 1, 2, 3 and 4) obtained by enzymatic digestion did not show homology with any of the known proteins in gene bank. Peptides NT, 1, 2 and 4 were found to mimic immunobiological activity of native protein. Passive administration of antibodies to peptides NT, 1, 2 and 4 induced infertility in male and female rats and peptide 1 was found to be most effective in suppressing fertility. Active immunization with keyhole limpet haemocynin (KLH) conjugated synthetic peptide 1 impaired fertility in all the male rabbits and six of the seven male marmosets. The fertility was restored following decline in antibody titre. All these findings on 80kDA HAS suggest that the synthetic Peptide-1 of 80kDa HSA is the promising candidate for development of male contraceptive vaccine.
  949 332 -
Regulation of luteinizing hormone receptor expression by an RNA binding protein: Role of ERK signaling
K.M.J. Menon, Bindu Menon
November 2014, 140(7):112-119
A specific luteinizing hormone receptor (LHR) mRNA binding protein (LRBP) has been identified and purified. This LH receptor mRNA binding protein selectively binds to the polypyrimidine rich bipartite sequence in the coding region of the LHR mRNA and accelerates its degradation. In response to preovulatory LH surge, the LH receptor expression in the ovary undergoes downregulation by accelerated degradation of LH receptor mRNA through the involvement of this RNA binding protein. Here we describe the intracellular mechanism triggered by LH/hCG (human chorionic gonadotropin) that leads to the regulated degradation of LH receptor mRNA. Downregulation of LH receptor mRNA was induced by treatment of cultured human granulosa cells with 10 IU of hCG. Activation of downstream target, extracellular signal-regulated protein kinase 1 and 2 (ERK 1/2) showed an increase within five min and sustained up to 1 h. Confocal analysis showed that ERK1/2 translocates to the nucleus after 15 min of hCG treatment. This leads to an increase in LRBP expression which then causes downregulation of LH receptor mRNA by accelerating its degradation. Treatment with UO126 or transfection with ERK specific siRNA (small interfering RNA) resulted in the abolishment of ERK activation as well as LHR mRNA downregulation. RNA electrophoretic mobility gel shift assay of the cytosolic fractions showed that hCG-induced increase in the LH receptor mRNA binding activity was also abrogated by these treatments. These results show that LH/hCG-induced LH receptor mRNA downregulation is initiated by the activation of ERK1/2 pathway by regulating the expression and activity of LH receptor mRNA binding activity.
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Regulation of assisted reproductive treatment (ART) in Australia & current ethical issues
Louise Johnson
November 2014, 140(7):9-12
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Delineating the prime mover action of progesterone for endometrial receptivity in primates
D Ghosh, J Sengupta
November 2014, 140(7):130-136
Progesterone is essential for endometrial receptivity in primates. It is now evident that embryo-derived signal influences implantation stage endometrium under progesterone dominance, and collectively results in endometrial receptivity to implanting blastocyst. Previously, a few studies were performed using global gene profiling based on microarray technology to identify changes in gene expression between early luteal phase and mid luteal phase endometrium, however, the issue of combinatorial regulation by progesterone-dependent regulation and by embryo-derived signal on transcripts profiles during endometrial differentiation toward receptivity for blastocyst implantation in primates has not been addressed. t0 he present review summarizes a few issues, specifically that of transforming growth factor β-tumour necrosis factor α (TGFβ-TNFα) pathways and signal transducer and activator of transcription (STAT) signalling system related to luteal phase progesterone action on endometrial receptivity in terms of its transcriptomic expression using a potent antiprogestin (mifepristone) in conception cycles of the rhesus monkey as a non-human primate model.
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Need for integration of gender equity in family planning services
Suneela Garg, Ritesh Singh
November 2014, 140(7):147-151
The family planning programme of India has shown many significant changes since its inception five decades back. The programme has made the contraceptives easily accessible and affordable to the people. Devices with very low failure rate are provided free of cost to those who need it. Despite these significant improvements in service delivery related to family planning the programme cannot be said to achieve success at all levels. There are many issues with the family planning services available through the public health facilities in India. Failure to adopt the latest technology is one of these. But the most serious drawback of the programme is that it has never been able to bridge the gap between the two genders related to contraceptives. The programme gave emphasis to women-centric contraceptive and thus women were seen as their clients. The choice to adopt a contraceptive though is 'cafeteria approach' in family planning lexicon; it is the choice of the husband that is ultimately practiced. There is not enough dialogue between husband and wife and husband and health worker to discuss the use of one contraceptive over another. The male gender needs to be taken in confidence while promoting the family planning practice. The integration of gender equity is to be done carefully so as not to make dominant gender more powerful. Only when there is equity between genders while using family planning services the programme will achieve success.
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