Fertility NEWS LETTER

Ideal fertility : ICSI / IVF & Genetic Center India

Dear Colleges
Hello

In this month we have our journal club and a young gynecologist of the city Dr.Anupama Solonki presented her topic on “ steroid synthesis and Two cell-two gonadotropin theory” . It was very basic in reproductive endocrinology and with new facts of paracrine and autocrine actions of various cytokines.

In the same context I presented one topic on clinical correlation of this theory in ovulation induction and ovarian stimulation.
Various facts of different drugs were discussed.

In this news letter I took two drugs ,which I found of interest ,one is clomiphene citrate and the other is GnRh antagonist.

I am really touched by the response I am getting for this news letter, I request you all to contribute in this endeavor to bring new clinical facts to our colleagues.

With best wishes
Dr. D’Pankar Banerji

1.Clomiphene citrate: Some useful points

Clomiphene acts as a competitive antagonist of 17beta estradiol at the level of the cytoplasmic nuclear receptor complexes in the hypothalamus, pituitary and elsewhere. Blockade of E2 receptor at eh level of hypothalamus leads to increase in gonadotropin –releasing hormone (GnRh) and to an increase in LH and presumably FSH.

FSH and LH rise is increased to 3-4 fold.

It requires an intact hypothalamus-pituitary-ovarian axis an destrogen

Due to its site of action the dose should be taken in one time to optimize its entry into hypothalamus.

After administration : A stedt state approximately 25%,of peak concentration is reached at 48 hrs. and remains constant fprthe next 14 days

Dose of clomiphene necessary to induce ovulation or increase luteal phase progesterone os proportional to body weight

The effect of repeated administration of a single 50mg tablet at 28 days interval is cumulative,wit basal level of zu-clomiphene omcreasing by 50% per month. Owing to the accumulation of zuclomiphene, clomiphene may be more effective in inducing ovulation during the second and later cycles of treatnment, even though the dose administered remains the same.

After ovulation induction with clomiphene, serum progesterone and estradiol serum levels are increasd during the luteal ppase of the cycle in a direct dose –response relationship.

Clomiphene citrate I given for 5 days,beginning from day 3- day5

Clomiphene is ineffective if started too soon,before estradiol level are 45-60 pg/ml. Follicles are 6 mm or greater when estradiol is in this range.

Starting dose should not be greater than 50 mg when weight is around 50 kg and should not be more than 100mg when around 75 kg.

Test required before starting clomiphene :

Ultrasound: Clomiphene should not be sarted if the endometrial lining is more than 6 mm,follicular response will be poor. It should be done to rule out any persistand corpus luteum,ovarian neoplasm,endometriosis and antral follicle count.

Ovarian cysts: cysts larger than 4 cm should be explored surgically,not drained. Smaller cyst without cancer chareacteristics of wall thickness 3 mm or greater or inclusions may either be followed until they resolve or suppressed with oral contraceptives.Progesterone alone is ineffective, and GnRh agonists may cause functional cysts to grow larger.

E2 and Progesterone : E2 > 45-60 pg/ml ,clomiphene will be effective. Raised progesterone will tell whether retension cyst is active or not. Before deciding that a patient is clomiphene resistant,E2 level should me measured on the customary start day to determine if clomiphene has been started too soon.

Monitoring :

Follicular development : In clomiphene cycle, the lead follicle is usually 20-24 mm the day ovulation and 18-20 mm the day of spontaneous LH surge.highest pregnancy rates occur when there are four follicles 15 mm or larger ad are not increased when five or more follicles.when HCG is used to trigger ovulation, highest pregnancy rates are achieved when the lead follicle is 16 mm.

Endometrial thickness : It should be at least 6 mm and preferably 9 mm or greater on preovulatory ultrasound. Endometrial thickness increases at a faster rate in clomiphene cycles than in spontaneous cycles durig the late proliferative phase as it escapes from antiestrogen effect of clomiphene.

Serum or urine LH : an increase in serum LH twice Vaseline level predicts ovulation within 24 hrs and urine LH predicts ovulation within 12 hrs.

Progesterone : It is used to confirm ovulation to determine if the dose of clomiphene is sufficient. It should be measured in midluteal phase5-7 days after ovulation,to conside with the day embryo inplantation. Progesterone levels in th midluteal phase of clomiphene cycles that result in term pregnancies average 37 pg/ml,compared to 22 pg/ml in spontaneous cycles. If it is found less in luteal phase then additional progesterone should be given to increase it above 20 pg/ml.

Intra-uterine insemination : IUI should be considered fpr women whose partner’s sperm only meets minimal standards for normal as well as women who have mucus abnormalities.

Unexplained infertility : use of clomiphene to increase pre-ovulation estrogen level and  post ovulation progesterone levels, alone or combined with IUI has been shown to be an effective first-line treatment for “unexplained infertility”. Diagnosis of luteal insufficiency can be missed if it is assumed that a progesterone level of 5 pg/ml is normal. In fact it should be more than 15 pg/ml.  

How many cycles of clomiphene should be performed: cumulative pregnancy rates after six cycles of clomiphene IUI reached 75% in women receiving donor semen and 65% in women treated with clomiphene for ovulatory dysfunction if they ere younger than forty two yrs, used sperm of satisfactory quality and did not have endometriosis or tubal factor

2. SUMMER COURSE PROGRAM

In Medical Biotechnology

7th June 2010 - 17th June2010
Time 8.00am-1.00pm

Program :

Day 1

Theory :

• Introduction to cell biology
• Microscopy

Practical :
Microscopy :Stereozoom, Trinocular photomicrography, Inverted Microscopy

Day 2

Theory

• Cell cycle and cell division
• Primary tissue culture, introduction to tissue culture

Day 3

Theory

1. Detection and measurement of genetic variation
2. Monohybrid/dihybrid, mutations, Mendelian genetics

Practical :
Planting

Day 4

Theory :

1. Replication
2. ranscription and translation

Practical :
DNA isolation from blood

Day5

Theory

1. ovulation induction for in vitro fertilization
2. Human ,genetic diseases

Practical :
PCR demonstration

Day6

Theory :
Embryo biotechnology and stem cells

Practical:

1. Hands on retrieval of mammalian eggs under stereomicroscope
2. in-vitro maturation of oocyte

Day7

Practical:
Harvesting of culture
In-vitro maturation of oocytes

Day8

Theory :
Single Gene disorders

Practical:
Cryopreservation of Spermatozoa and oocytes

Day9

Theory :
Immunogenetics,basic

Practical:
Banding / slide preparation /identification of chromosomes harvested earlier

Day10

Seminar by the participants
Certificate distribution

Faculty :
1. Dr.D'Pankar Banerji, Gynecologist and Infertility specialist
2. Dr. Mrs. Rinku Banerji ,Pathologist and Embryologist

Fees : Rs.5000.00
Phone Number to contact : 2627711
Stay can be arranged at nearby hotels at a reasonable rates at an extra cost