Prevalence of Polycystic Ovarian Syndrome in Nepal

                                                                                                           Dr. Uma Shrivastava 

                                                                                          Infertility Centre, Bijulibazar, Kathmandu

Introduction   

• Most common cause of female infertility
• (Nestler JE Fertil. Steril:77: 209 March 2002)                                                              
• Presents with Anovulation & Infertility
• Multiple small cortical follicles with typical necklace like appearance in both ovaries
• Vague multi-systemic endocrine disorder
• High level of hormones LH: FSH ratio, DHEAS, Prolactin, TSH, Insulin etc.
• By the age of 40 years up to 40% of women may develop type 2 diabetes or impaired glucose tolerance
• Women with PCOS are at the risk of MI & heart disease seven times more than normal women
                     

Prevalence rate 

• Among women of reproductive age 28-31%
(Knochenhauer ES. J Clin Endocrinol Metab. 1998 Sep;83(9):3078-82 & 2000 Jul;85(7):2434- 8)
• Among obese women 28-30%
Alvarez-Blasco F. Arch Intern Med. 2006 Oct. 23;166(19):2081-6)
• Among Hirsute 23%
(J Clin Endocrinol Metab. 2000 Vol. 85, No. 11 4182-4187)
• Among Frank diabetics 33%
(Fertil Steril. 2006 Aug;86(2):405-10. Jun8)
• Genetic link –affected sisters up to 80%
(Fertil Steril. 2001 Jan;75(1):53-8)
• Among ischaemic heart disease 46%
(MJA 1998; 169: 537-540)

Signs & Symptoms 

• Anovulation
1. Early Cycle
2. Regular Cycle
3. Late Cycle
• Obesity
• Hirsutism
• Acne
• Alopecia
• Acanthosis nigricans

 Etiology 

• Clearly unknown – an Enigma
• Insulin resistance
• Hyper-secretion of Lutenizing hormone
• Hyperandrogenism
• Genetic predisposition  

 Pathogenesis

 I. Insulin Resistance
• Normally glucose is passed into the cell through insulin receptors doorway
• The average healthy body contains 20,000 insulin receptor sites per cell
• The average overweight individual with PCOS can have as few as 5,000 insulin receptor sites
• In PCOS few receptor sites will not allow all the glucose into the cell
• Glucose remains in the blood stream
• Glucose is converted into fat and stored via the blood stream throughout the body
• Excess fat lead to weight gain and obesity

II. Increased peripheral Estradiol & estrone levels
• Stimulates numerous follicular growth
• Some follicles undergo luteinization
• Stimulates stroma & theca of ovary, increase surface
• Multiple follicles surrounded by hyperplastic theca
• Some follicles remain stunted & few undergo atresia
• Prevent normal follicular development - Anovulation !
III. Androgen excess
• Stimulates stroma & theca of ovary, increase surface
• Multiple follicles surrounded by hyperplastic theca
• P450 aromatase gene mutation
• Production of excess Androgen & testosterone

IV.  Abnormal gonadotropin dynamics
• Altered diurnal rhythm of LH secretion
• Increased LH pulse frequency
• Stimulates numerous follicular growth
• Feedback increase in FSH
• More new follicles growth
• Accelerates LH production & suppress FSH
• Elevated LH:FSH ratio

Materials & Methods

• Retrospective study conducted at the Infertility & IVF Centre, Kathmandu
• A counseling & laboratory based study
• Duration (Sept. 2003 - Nov. 2006)
• The study population- women willing to conceive & adolescence with irregular menstrual cycle
• Total female analyzed = 3740

 PCOS diagnostic criteria

A. Symptomatic (Counseling)
• Irregular cycle
• Positive family history
• Hirsutism
• Obesity
B. Laboratory Evaluation
• High level of hormones (LH, Insulin, Androgen, Prolactin, Estrogen etc.)
• Ultrasonic evaluation – Abdominal & trans-vaginal ultrasonography of the ovaries
•       Black pearl necklace-like appearance of multiple cortical cysts
• Ovarian volume of more than 10 cm3
C. Exclusion of secondary causes
       

Management of PCOS

• Ovulation induction - Clomiphene citrate , FSH, GnRH etc.
• Insulin sensitizing agents – Glucophase, Pioglitazone, D-chiro inositol etc.
• Weight reduction - Diet management
• OC pills
• Ovarian volume reduction-Surgical procedure

Conclusion

Previous studies          

• Up to 31% prevalence PCOS
(Asuncion M. J Clin Endocrinol Metab. 2000 Jul;85(7):2434-8)
• Higher prevalence in Indian than Chinese ethnic
       (Williamson K. Aust N Z J Obstet Gynaecol.2001 May;41(2):202-6)

Our study (Infertility Centre)

• Total female analyzed = 3740
• Hormonal & other disorder = 2200 (58.9%)
• Structural & functional PCOS = 1500 (40%)
• Cut off = 40
• About 400 PCOS (40%) in 1000 reproductive disorders
• More studies needed in this area

                                                                      (Paper presented at NESOG Conference 2007)

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Nepali ‘test-tube baby’ could become a reality

By Suvecha Pant
Kathmandu Post
KATHMANDU, July 9 2002.
What can be termed as a breakthrough in science and technology in Nepal, "test-tube" baby production is underway for couples who are without children or who have not had one for a long time.
A treatment centre at Putalisadak, Kathmandu, which for over eight years has been helping treat infertile males and females, from Sunday has begun the initial stages of producing test-tube babies for couples without children. Already two childless women are beginning the initial tests.
"This is good news for the fifteen percent of the population in Nepal who are childless" said Dr. Uma Shrivastava, working at the Infertility Research Centre. She further added that equipment required for the production of test tubes had been brought and the research to produce the first test-tube baby in Nepal was underway.
So, how are test-tube babies produced? "In Vitro Fertilisation (IVF) or test-tube babies are the basic assisted reproduction technique in which fertilisation occurs in vitro (literally in glass)," explained Shrivastav. She further added that the man’s sperm and the woman’s egg are combined in a laboratory dish, and after fertilisation, the resulting embryo is then transferred to the woman’s uterus.
"The five basic steps in an IVF treatment cycle are superovulation (stimulating the development of more than one egg in a cycle), egg retrieval, fertilisation, embryo culture, and embryo transfer," said Shrivastav adding that the stimulation period would begin by August.
"IVF will benefit Nepali couples that are not able to conceive for various reasons and presently have to travel to India spending hundreds of thousands of rupees," said the doctor who is also a masters degree holder from the University of London in Reproductive Endocrinology. "Although some of these couples have given birth to children, there are still many women who have had to return without conceiving."
Therefore, at a cheaper price than India, the centre plans to provide the same services of IVF. However, IVF is not a foolproof solution, warns Shrivastav. "IVF does increase the chances of conceiving as it is assisted reproduction in which the doctor lends a helping hand to the natural process, and the success rate is around 20 per cent."
Inspite of this, for those parents who are without children, even this success rate brings some sense of hope.
Although very common in developed nations, both the lack of highly trained doctors in Nepal and the expense of producing test-tube babies have restricted its use.
Travelling back in history, the first test-tube baby was born in England only 20 years ago. This birth through in vitro fertilisation revolutionised medical treatments for infertility, making it possible for thousands of women to conceive.

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Quiz Case

Infertility Centre

A 32 yrs. old healthy looking, actively working for women development lady visits Infertility Centre with complaints of missed period for about three months. She also complained of no issue with eight years of married life. She does not have any significant medical history. In the menstrual history, she got her menses at the age of sixteen. Since then, the cycle is irregular which comes at the interval of 40 days to 10 months period. During menses she has very scanty flow for about four days. She often has abdominal discomfort during flow period. She has two sisters who were not married. She does not smoke nor drinks.

Her husband 33 yrs old, physically active & has one elder brother who has two children. He drinks alcohol only during weekend but does not smoke.

 Physical examination of the lady: General look fair; weight = 48kg; height = 5'2''; B.P. 110/70mmHg. She had normal female type hair growth, normal breasts & female type voice. Pelvic examination showed normal vulva & vagina. Per speculum examination showed the cervix was normal size but little pale. On per manual examination, uterus  anteverted, normal sized, adnexae free. Thus she was found to be a physically a normal lady.

Hemogram: HB = 10.8; TC = 7000; N = 68 ; L = 20; E = 7 ; M = 5 ; ESR = 16 mm/hr

Urinanalysis: Nothing significant

Hormone profile on D2: FSH = 43.1mIU/ml; LH = 6.4 mIU/ml; Prolactin = 112.9; Estradiol = 16.6 pg/ml; TSH = 2.0 mIU/ml

Her HSG showed patent both fallopian tubes.

Basal ultrasound with transvaginal probe showed both ovaries with immature follicles. The uterus was slightly small in size with midline endometrium.

This lady was treated only for two cycles for conception. She has a healthy baby boy & is living very happy life. 

Can anyone outline the treatment for her conception?

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