ObGyn Watch October 2004 R Narayanan OCTOBER 2004

Nitric Acid (N.O) in Female Reproduction

N.O - Major Paracrine Mediator & Regulatory Agent  Menstruatio n  Ovulation  Endometrial receptivity  Implantatio n  Maintenance of Pregnancy  Cervical Ripening  Tocolysis  Labour Pains N.O Donors promote Fertility & Inhibitors facilitate Contraception Maul H et al Curr Pharm Design Feb 2003

Effect of N.O on Vasculature  N.O Promotes Vasodilatation & inhibits Platelet Aggregation  Low N.O in early II Trimester impairs vascular formation leading to Placental insufficiency & FGR  High N.O in III Trimester represents compensated Pl perfusion in IUGR  PE develops due to dysfunction of L-arginine – N.O pathway Tranquilli AL et al J Mat Fet NN Med

Effect of L-arginine  L-arginine infusion decreases BP in Normo as well as Hypertensive mothers  Reduces BP through release of N.O  Improves endothelial function  Inhibits Platelet aggregation  Prevents Pre eclampsia  Potent relaxant - Prolongs pregnancy  Better Perinatal outcome Alfredo et al Rev Chil Ultrasono 2001

Doppler – USG Evaluation  Lowers Uterine artery vascular resistance  Pathological Doppler waveforms paralleled with N.O production  Accelerated fetal Growth in Rx Group  Birth weight improved Sieroszewski P et al J Mat Fet NN Med June 2004

Oral 0.1G/Kg/Day X 2 weeks From 10 th Gestational Week

Moderate intake of Coffee has No effect on Abortion -Coll PN Project Klebenoff et al N Eng J Med 1988 Coffee >150G/day increases RR Spontaneous Abortion to 1.36 & LBW to 1.5 Meta analysis of 32 studies High Coffee intake increases Sudden Infant Death Syndrome Ob Gyn Surv 1999 Retrospective study 562 Spont Aborters compared with 953 matched controls: Increased coffee consumption increases abortion risk – Coffee not Mutagenic -Cnattingius S Sweden N Eng J Med 2000

During Pregnancy It is safe to consume Less than 150G Coffee/Day Which is equal to: 1 cup of Brewed 2 cups of Instant 3-4 cups of Tea 2-3 Soft Drinks

How about Tea? Study of >1000 women 30 & Older in Taiwan Average of 2 cups of Tea >10 years 6.2% greater Bone Density Fluorides,Flavonoids & Phytoestrogens responsible Tea has >4000 Health- affecting Compounds

Polycystic Ovaries  Incidence of Abortion in PCOS: 30-50%  Causes: 1.Elevated LH 2.Hyper insulinemic Insulin Resistance 3.Elevated Androgens 4.CL Deficiency following Dysovulation

Metformin  Insulin Resistance  Serum Androgen  Improves Ovulation  Abortion  Obesity

Retrospective Study of Metformin in Pregnancy  Metformin 1-2 G / day throughout Pregnancy  Abortion Rate : 9% in study group (42% in controls)  Lower Free Testosterone levels  No IUGR  No Fetal Anomalies Daniela DJ et al J Endocrin Metabol 2002

Metformin & GDM  Prospective & retrospective Study  Incidence of GDM: 3% in Study group (23% in Controls)  Safe in Pregnancy  Probably acts by decreasing secretory demands on Pancreatic beta cells Glueck et al 2001

L’scopic Ovarian Drilling  In CC Resistant PCO:  Spont Ovulation 57%  Conception 50%  Reg Cycles >1 yr 50%  Poor Responders: BMI >35Kg/m2 Testosterone >4.5 nMol/L Infertility >3 yrs Hum Repr 2004

Farquhar C et al Cochrane Library Issue 3, Trials of L’scopic Drilling Vs GTH Induction: Compared 6-12 mths following Drilling with 3-6 cycles of GTH Cumulative Pregnancy Rate Same Miscarriage rate same Multiple pregnancy less with Drilling

American Men shave 48 sq inches 24 times/month Women, 412 sq inches 11 times/month -Gillette -Westinghouse 1941

Dysmenorrhoea  Pain Relief: Naproxen 59% Ibuprofen 70% Mefanemic Acid 69% Aspirin 29%  Ibuprofen drug of choice  Coxibs=Naproxen Metanalysis: Double Blind RCTs Zhang WY et al Br J Ob G 1998

Source BMJ 1999

Eminence-Based Medicine ‘The more senior the physician, the less important the evidence!’ “Clinical Experience” is defined as ‘Making the same mistakes With increasing confidence over an impressive number of years’

Vehemence-Based Medicine ‘Substitution of volume For Evidence!’

Eloquence-Based Medicine ‘Smooth tongue, Sartorial elegance And Verbal eloquence are Powerful Substitutes’

Providence-Based Medicine ‘Decision may best be left In the hands of Almighty!’

Diffidence-Based Medicine ‘A sense of Despair Makes the physician feel helpless And do nothing!’

Nervousness-Based Medicine ‘Fear of Litigation Leads to over investigate And over treat!’

Confidence-Based Medicine (Restricted to Surgeons) ‘He will let his scalpel speak!’

One-day old TAMARA – 3.75 Kg With Mother 32 year old Quarda Touriat at Brussels On 24 Sep ‘04 Prof Donnez froze Touriat’s ovaries in 1997 before Chemo/Radio Rx for Stage IV Hodgkins Lymphoma. Laparoscopic Ovarian Transplant in 2003 Menstruation returned 4 months later. Conceived naturally -Lancet Sept’04 Stop Press!