First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis.

Hum Reprod Update. 2019 Nov 5;25(6) : 717-732. Doi: 10.1093/humupd/dmz029.

Wang R1,2,Li W2, Bordewijk EM3, LegroRS4, Zhang H5, Wu x6, Gao J6, Morin-Papunen L7, Homburg R8, Konig TE9, Moll E 10, Kar S11, Huang W12, Johnson NP1,13, Amer SA 14, Vegetti W15, Palomba S16, Falbo A17, Ozmen U18,Nazik H19, Williams CD20, Federica G21, Lord J22, Sahin Y23, Bhattacharya S24, Norman RJ1,25, Van Wely


Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: a regional cross-sectional study.

Am J Obstet Gynecol. 2017 Aug; 217(2):189.e1-189.e8.doi:10.1016/j.ajog.2017.04.007.Epub 2017 Apr 8.Am J Obstet Gynecol.

Chan JL 1, Kar S2, VenkyE3, Morin-Papunen L4, Piltonen T4, Puurunen J5, Tapanainen JS6, Maciel GAR7, Hayashida SAY7, Soares JM Jr7,Baracat EC7, Mellembakken JR8, Dokras A9.


TRPV4 is endogenously expressed in vertebrate spermatozoa and regulates intracellular calcium in human sperm

Transient Receptor Potential Vanilloid sub-type 4 (TRPV4) is a non-selective cationic channel involved in regulation of temperature, osmolality and different ligand-dependent Ca(2+)-influx. Recently, we have demonstrated that TRPV4 is conserved in all vertebrates. Now we demonstrate that TRPV4 is endogenously expressed in all vertebrate sperm cells ranging from fish to mammals. In human sperm, TRPV4 is present as N-glycosylated protein and its activation induces Ca(2+)-influx. Its expression and localization differs in swim-up and swim-down cells suggesting that TRPV4 is an important determining factor for sperm motility. We demonstrate that pharmacological activation or inhibition of TRPV4 regulates Ca(2+)-wave propagation from head to tail. Such findings may have wide application in male fertility-infertility, contraception and conservation of endangered species as well.

Ashutosh Kumara, Rakesh Kumar Majhia,1, Nirlipta Swaina,b,1, S.C.Giric, Sujata Kard, Luna Samantab, Chandan Goswamia,*

Keywords: Calcium-wave; Evolution; Sperm; TRP channels; TRPV4; Vertebrates.

Comprehensive treatment of high risk maternal diseases like diabetes, hypertension, heart, kidney, liver disease , blood thrombophilias, sickle cell disease, RH isoimmunization and cancer survivors And Fetal congenital abnormalities, genetic diseases, twins, triplets with sophisticated testing such as Prenatal biochemical screens, amniocentesis, chorionic villus sampling, NIFTY (non invasive fetal trisomy), targeted fetal anomaly screening, high risk level three sonographies, fetal echocardiography.Lady Gynecologist Doctors in Bhubaneswar Odisha DR SUJATA KAR.



Histone retention, protein carbonylation, and lipid peroxidation in spermatozoa: Possible role in recurrent pregnancy loss

Contribution from a defective paternal genome has been attributed to be an important cause for spontaneous recurrent pregnancy loss (RPL). Increased oxidative stress results in decreased detoxification and is a cause for damage to chromatin, proteins, and membrane lipids. The present study aimed to explore if there is a significant relationship between retained histones due to defective packaging of DNA in spermatozoa and oxidative stress. RPL patients (n=16) with a history of ≥2 embryo losses before the 20th week of gestation and no female factor abnormality, and fertile healthy volunteers (n=20) as controls were included in the study. A significant difference in the levels of protein carbonylation and lipid peroxidation together with an increased retention of histones in the experimental groups was noticed. Histone carrying sites for oxidative modification such as arginine and lysine might be responsible for disturbing the paternal epigenomic control during early stages of embryonic differentiation leading to abortion.

Results and discussion

The semen was viscous and had a pH within the range of 7.0-8.0 in both the control and RPL groups. Routinely analyzed sperm attributes except sperm count and leukocyte concentration showed a distinct significant change in the RPL group (Table 1). The percentage of motile spermatozoa drastically dropped in the RPL group but it was still possible to achieve pregnancy as it is above the lower reference limit of 40% [WHO 2010]. However, the oxidative stress parameters of semen showed a significant increment in the RPL patient group

Gatatri Mohantya,*, Nirlipta Swaina,b,*, Chandan Goswamib, Sujata Karc , and Luna Samantaa

As an experienced Endo-ART specialist, to date has done more than 10000 cases of advanced Gynaecologic endoscopic surgery & Assisted Reproduction. She is the recipient of many prestigious awards for her achievements in the field of Gynaec Endoscopy.Dr Sujata Kar Best Laparoscopic Surgeons in Bhubaneswar Odisha


Clomiphene citrate or letrozole as first-line ovulation induction drug in infertile PCOS women: A prospective randomized trial.



To compare Letrozole (5 mg) and clomiphene citrate (100 mg) as first line ovulation induction drug in infertile PCOS women.


Prospective Randomised trial.


A Tertiary level infertility centre.


103 infertile PCOS women.


Treatment naïve infertile PCOS women were randomised to treatment with 5 mg letrozole (51 patients) or 100 mg clomiphene citrate (52 patients) daily starting day 2 to day 6 of menstrual cycle. Timed intercourse or Intra Uterine Insemination (IUI) was advised 24 to 36 hours after Human Chorionic Gonadotropin (HCG) injection.


Ovulation rate, mono or multi follicular rate, days to ovulation, endometrial thickness, serum progesterone, serum estrogen, pregnancy rate, miscarriage rate.


The mean age, Body Mass Index (BMI), duration of infertility in both Clomiphene Citrate (CC) and Letrozole groups were similar.Ovulation rate was 73.08% in letrozole group and 60.78% in CC, which was not statistically significant (P=0.398). There was no statistically significant difference between Endometrial thickness (CC 7.61 ±1.96, Let 7.65 ± 2.10), Sr E2 on day of HCG (CC 178.3 ± 94.15, Let 162.09 ± 73.24), Days to ovulation (CC 14.2 ± 3.41; Let 13.13 ± 2.99) and Sr P4 on D21 (CC 10.58 ± 6.65; Let 11.86 ± 6.51). Monofolliculo genesis (CC 54.84, Let 79.49 %, P=0.027) and Pregnancy rate (CC 7.84%, Let 21.56% P=0.0125) were statistically significantly higher in letrozole group.


Our study shows that letrozole has excellent pregnancy rates compared to clomiphene citrate. Letrozole should be considered at par with clomiphene citrate as first line drug for ovulation induction in infertile PCOS women.


Clomiphene citrate; PCOS; letrozole; ovulation induction


Assisted reproduction in polycystic ovarian disease: A multicentric trial in India.



The aim of this study is to compare ovarian response, oocyte, embryo quality, ovarian hyperstimulation syndrome incidence, and pregnancy rates in polycystic ovary syndrome (PCOS) and non-PCOS group.


This was a prospective observational study on PCOS carried out in seven assisted reproduction centers in India between August 2008 and July 2010, as part of trial under the Indian Society of Assisted Reproduction. A total of 192 women (77 in the PCOS group and 115 in the non- PCOS group) undergoing in vitro fertilization/intracytoplasmic sperm injection were included. All women had long protocol and recombinant follicle-stimulating hormone stimulation.


The mean number of follicles and oocytes was higher in PCOS group compared with non-PCOS, being 27.2 (±8.8) and 13.6 (±5.3); 15.9 (±6.3) and 10.9 (±6.2), respectively. The recovery rates of oocytes and mature oocytes per follicle were less in the PCOS group which was 64% and 61.1%, respectively as opposed to 80.3% and 74.5%, respectively in non-PCOS group. The total numbers of top-quality embryos were less in the PCOS group.


In PCOS women though the number of follicles was more, recovery of mature oocytes, top-quality embryos was less. Pregnancy rates were comparable in both groups.


Fertilization response to ovulation induction; polycystic ovary syndrome


Current evidence supporting “letrozole” for ovulation induction.


Aromatase inhibitor “letrozole” was first introduced as a potential ovulation induction (OI) drug almost a decade back. Large number of studies has been published using letrozole for OI: In polycystic ovary syndrome (PCOS) women, clomiphene citrate (CC) resistant women, for intrauterine insemination and also in various protocols of mild stimulation for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Letrozole appears to be a good option, with its oral route of administration, cost, shorter half-life and negligible side effects. However, the verdict on efficacy and safety of letrozole is still uncertain. This review explores the current scientific data supporting letrozole for OI.


Aromatase inhibitor; congenital malformations; letrozole; ovulation induction


Anthropometric, clinical, and metabolic comparisons of the four Rotterdam PCOS phenotypes: A prospective study of PCOS women.


1. To study the distribution of various Rotterdam classified phenotypes of polycystic ovarian syndrome (PCOS) women, in our population. 2. To compare the four phenotypes with respect to anthropometric, clinical, and metabolic parameters. 3. To report the prevalence of insulin resistance (IR) and metabolic syndrome in these women.


Private practice, Prospective cross-sectional comparative study.


Women attending gynecology outpatient with the primary complains of irregular menses and/or infertility were evaluated. Each of them underwent detailed clinical examination, transvaginal sonography, and biochemical and hormonal assays. Four hundred and ten women with a clinical diagnosis of PCOS based on Rotterdam criteria were included in the study. The four phenotypes were 1) PCO complete, that is oligo/anovulation (O) + polycystic ovaries (P) + hyperandrogenism (H) 2) P + O, 3) P + H, and 4) O + H. All women were also evaluated for metabolic syndrome (American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI), modified Adult Treatment Panel (ATP) III 2005 guidelines) and IR (homeostatic model assessment-IR (HOMA-IR)).


Statistical Package for Social Sciences (SPSS) version 18.


Largest group was PCOS complete (65.6%) followed by P + O (22.2%); H + O (11.2%); and P + H (0.9%). Overall prevalence of metabolic syndrome was 35.07%. Hyperandrogenic phenotyptes; H + O (50%) and P + H + O (37.04%), had significantly higher prevalence of metabolic syndrome than normoandrogenic P + O phenotype (10%) (P ≤ 0.001). Body mass index (BMI) ≥ 25 (P = 0.0004; odds ratio (OR) = 3.07 (1.6574-5.7108, 95% CI)), waist circumference (WC) ≥ 80 cm (P = 0.001; OR = 3.68 (1.6807-8.0737, 95% CI)) and family history of diabetes (P = 0.019; OR 1.82 (1.1008-3.0194, 95% CI)), were strongly associated with the presence of metabolic syndrome. The overall prevalence of IR in PCOS women was 30.44% (HOMA-IR cutoff ≥ 3.8) and 34.94% (HOMA-IR cutoff ≥ 3.5).


The prevalence of metabolic syndrome and IR was 35.07 and 30.44%, respectively. The hyperandrogenic phenotypes have significantly higher metabolic morbidity compared to normoandrgenic phenotype. BMI > 25, WC ≥ 80 cm, and family history of diabetes carry the highest risk for developing metabolic syndrome.


Insulin resistance; metabolic syndrome; phenotypes; polycystic ovarian syndrome


Clomiphene citrate, metformin or a combination of both as the first line ovulation induction drug for Asian Indian women with polycystic ovarian syndrome: A randomized controlled trial.


To compare clomiphene citrate (CC), metformin or the combination of CC and metformin as the first line ovulation induction drug in Asian Indian women with polycystic ovary syndrome (PCOS).


One hundred and five newly diagnosed, treatment naive PCOS women were recruited. They were randomized into any of the three groups: Group I (CC 50-150 mg/day), Group II (metformin 1700 mg/day), and Group III (CC + metformin in similar dosage to Groups I and II). Patients underwent follicular monitoring and advice on timed intercourse. The study period was 6 months, or till pregnant, or till CC resistant. Primary outcome studied was live birth rate (LBR). Secondary outcomes were ovulation rate, pregnancy rate, and early pregnancy loss rate.


There was no significant difference among the groups in baseline characteristics and biochemical parameters. LBR was 41.6%, 37.5%, and 28.1%, respectively in Groups III, II, and I. Group III (CC + metformin) had the highest ovulation (83.3%), pregnancy (50%), and LBRs (41.6%). Group II (metformin) was as good as Group I (CC) in all the outcomes. CC + metformin (Group III) had statistically significantly higher ovulation rate as compared to CC alone (Group I) (P = 0.03; odds ratio: 95% confidence interval: 3.888 [1.08-13.997]).


Thus, our study shows that metformin was as good as CC in terms of “LBR” and the combination of CC and metformin gave the highest ovulation and LBR.


Clomiphene citrate; metformin; ovulation induction; polycystic ovary syndrome; pregnancy rate