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Jana S.K.,Indian Institute of Technology Kharagpur | Banerjee P.,Indian Institute of Technology Kharagpur | Mukherjee R.,Indian Institute of Technology Kharagpur | Chakravarty B.,Institute of Reproductive Medicine | Chaudhury K.,Indian Institute of Technology Kharagpur
Journal of Assisted Reproduction and Genetics | Year: 2013

Purpose: To investigate the Homeobox genes HOXA-10 and HOXA-11 mediated endometrial molecular defects during implantation window in endometriosis- associated infertility cases. Methods: Endometrial biopsies were obtained during implantation window from 31 infertile women with endometriosis (age < 35 years) and 26 age and BMI-matched infertile women without endometriosis were included in the study for comparison purposes. Endometrial expression of HOXA-10 and HOXA-11 genes, MMP-2, -9, αvβ3 integrin, leukemia inhibitory factor and surface characteristics including average roughness and topology were assessed. Results: A significantly lower expression of HOXA-10 and HOXA-11 were observed in endometriotic women compared to non-endometriotic controls. Further, a significantly higher endometrial expression of MMP-2 and -9 were observed in women with endometriosis when compared with controls. Interestingly, endometrial surface were observed to be grossly affected in terms of average roughness and topology in women with endometriosis compared to controls. Conclusions: The findings suggest that aberrant expression of HOXA-10 and -11 genes adversely affects endometrial remodelling and expression of receptivity markers. © 2013 Springer Science+Business Media New York.

Dons'koi B.V.,Ukrainian Academy of Sciences | Chernyshov V.P.,Ukrainian Academy of Sciences | Sirenko V.Y.,Institute of Reproductive Medicine | Strelko G.V.,Institute of Genetic of Reproduction | Osypchuk D.V.,Ukrainian Academy of Sciences
Immunobiology | Year: 2014

Problem: NK lymphocytes play critical yet poorly defined role in implantation and during development in early pregnancy. Methods of study: Recently, we showed that the proportion of NK that expressed CD69+ after incubation with K562 (CD69stim) cells reflected the NK population excitation potential. In the present study, we investigate the significance of NK activation levels in predicting embryo implantation. Results: A qualitative analysis of values distribution in two groups showed that 25/33 (75.8%) women who became pregnant had CD69stim levels that were >30 but <60% (conditionally normal zone). In contrast, CD69stim levels in patients who failed to become pregnant were either elevated, as in 10/51 (19.6%), or reduced, as in 20/51 (39.2%) of the patients. Accentuated CD69stim levels were predictive for implantation failure, extremely significant for decreased (OR 6.9, p=0.0004) and not quite significant for increased CD69stim levels (OR 3.9, p=0.062). Accordingly, conditionally normal CD69stim levels were favourable for implantation (OR 4.46, p=0.0032). Conclusion: We confirm that actual peripheral blood natural killer cells activation status have an influence on embryo implantation. We showed that exactly normal NK cell activity predicting successful implantation. © 2013 Elsevier GmbH.

Chakraborty P.,Institute of Reproductive Medicine | Goswami S.K.,Institute of Reproductive Medicine | Rajani S.,Institute of Reproductive Medicine | Sharma S.,Institute of Reproductive Medicine | And 3 more authors.
PLoS ONE | Year: 2013

Recurrent pregnancy loss (RPL) in polycystic ovary syndrome (PCOS), which occurs in ∼50% of total pregnancies is a frequent obstetric complication. Among the several hypotheses, insulin resistance (IR), obesity and hyperhomocysteinemia (HHcy) play significant role/s in RPL. This study was conducted to assess the link between elevated levels of homocysteine and IR in PCOS-associated women with RPL in Kolkata, India. A retrospective study was conducted of one hundred and twenty six PCOS women (<30 years) who experienced two or more spontaneous abortions during the first trimester presenting to Institute of Reproductive Medicine (IRM) in Kolkata during the period of March 2008 through February 2011. One hundred and seventeen non-PCOS subjects with matching age range were randomly chosen as controls. Incidence of HHcy and IR was 70.63% (n = 89) and 56.34% (n = 71), respectively, in RPL-affected PCOS population which was significantly higher (p<0.04; p<0.0001) when compared to the non-PCOS set (HHcy: 57.26%; IR: 6.83%). Rates of miscarriage were significantly higher (p<0.008; p<0.03) in hyperhomocysteinemia-induced miscarriage when compared to the normohomocysteinemic segment (PCOS: 70.63% vs.29.36% & non-PCOS: 57.26% vs. 42.73%) along with the insulin resistant (p<0.04; p<0.0001) population (PCOS: 70.63% vs. 56.34% & non-PCOS: 57.26% vs. 6.83%) in both groups. A probabilistic causal model evaluated HHcy as the strongest plausible factor for diagnosis of RPL. A probability percentage of 43.32% in the cases of HHcy- mediated RPL suggests its increased tendency when compared to IR mediated miscarriage (37.29%), further supported by ROC-AUC (HHcy: 0.778vs. IR: 0.601) values. Greater susceptibility towards HHcy may increase the incidence for miscarriage in women in India and highlights the need to combat the condition in RPL control programs in the subcontinent. © 2013 Chakraborty et al.

Subramani E.,Indian Institute of Technology Kharagpur | Subramani E.,McGill University | Madogwe E.,McGill University | Ray C.D.,Post Graduate Institute of Medical Education and Research | And 5 more authors.
Fertility and Sterility | Year: 2016

Objective To investigate the influence of dormant Mycobacterium tuberculosis on the expression of various endometrial receptivity markers and leukemia inhibitory factor (LIF)-signal transducers and activators of transcription 3 (STAT3) signaling pathway. Expression of endometrial receptivity markers and LIF-STAT3 signaling in in vitro decidualized human endometrial stromal cells (hESC) treated with 65 kDa mycobacterial heat shock protein (HSP65) is also explored. Design A prospective study. Setting Tertiary care hospital and reproductive health research unit. Patient(s) Endometrial tissue samples were collected from 38 women who tested positive for Mycobacterium tuberculosis and 30 normal women with proven fertility undergoing sterilization. In vitro decidualization of hESC was performed. Intervention(s) Endometrial biopsies collected from all women during implantation window and treatment of hESC with HSP65. Main Outcome Measure(s) Measurement of various endometrial receptivity markers including αvβ3 integrin, E-cadherin, MECA-79, mucin-1, and pinopodes and LIF/LIFR-STAT3 signaling molecules expressed in the endometrium of women with dormant genital tuberculosis (GTB) during implantation window and measured also in HSP65-treated hESC. Result(s) Significantly reduced levels of endometrial receptivity markers LIF, LIFR, and pSTAT3 were observed in endometrium of women with dormant GTB as compared with controls. A similar trend was observed under in vitro conditions with decreased level of phosphorylated STAT3 in HSP65-treated hESC. However, no change in the expression of endometrial receptivity markers under in vitro conditions was observed. Conclusion(s) Our findings suggest that endometrium of women with dormant GTB is associated with poor receptivity, as evidenced by reduced receptivity markers and aberrant LIF-STAT3 signaling. In vitro treatment of hESC with HSP65 also confirms compromised endometrial decidualization. © 2016 American Society for Reproductive Medicine.

Singh A.K.,Indian Institute of Technology Kharagpur | Chattopadhyay R.,Institute of Reproductive Medicine | Chakravarty B.,Institute of Reproductive Medicine | Chaudhury K.,Indian Institute of Technology Kharagpur
Fertility and Sterility | Year: 2013

Objective: To investigate differences in the activity of matrix metalloproteinases (MMPs) 2 and 9 and their respective tissue inhibitors (TIMPs) in follicular fluid of women with endometriosis, to correlate the findings with IVF outcome, and to examine the therapeutic potential of progesterone supplementation in restoring the fine balance between MMPs and TIMPs. Design: Prospective case-control clinical study. Setting: Infertility clinic and reproductive health research unit. Patient(s): A total of 340 infertile women undergoing IVF. Intervention(s): Natural micronized progesterone capsules were administered for luteal support. Main Outcome Measure(s): Association of MMPs 2 and 9 and TIMP-1 with oocyte maturity and embryo development. Result(s): An abnormal expression of MMP-2, MMP-9, and TIMP-1 with extensive MMP-9/TIMP-1 imbalance in women with endometriosis undergoing IVF was observed. Transforming growth factor β1 plays an important role in these women with possible involvement of Smad-2 and -3 proteins. Progesterone supplementation improves the imbalance in MMP-9/TIMP-1 ratio significantly in women with endometriosis who conceive after IVF. Conclusion(s): Increase in MMP-2 and -9 and decrease in TIMP-1 expression was associated with poor oocyte and embryo development in women with endometriosis undergoing IVF. MMP-9/TIMP-1 balance was highly affected in these women, and progesterone supplementation appeared to restore this imbalance to a considerable degree. Copyright © 2013 Published by Elsevier Inc.

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