Fertility NEWS LETTER

Ideal fertility : ICSI / IVF & Genetic Center India

Dear Colleges
Hello

In this issue I am touching two topics which baffles me a lot. One is PCO and other is hypothalamic amenorrhea.

It is really very difficult to treat a PCO esp. when they come for IVF. They behave very differently than the normo-gonadotrophic females. Most of them are obese and few of them are of normal weight. Insulin resistance is now an established  reason with PCO. When we ask the obese one to loose weight ,they find it difficult, when you see a lean PCO ,then again question comes why this lean lady has PCOS. It is like endometriosis or eclampsia, where we treat the patient but do not know what we are treating.

Stimulating the PCOS with clomiphene or letrosole or gonadotrophins are not well predicted. They may not get stimulated or may hyper-stimulate. Results of embryo implantation is very low, but the same embryos when they are transferred to a recipient they give good pregnancy rates. Eggs may be good but endometrium may be at fault in PCOS.

Recently I came across to few cases of Hypogonadotrophic amenorrhea patients . In most of them I found Body mass index is on lower side  and they present to me for infertility. It is easy to treat a hypothalamic amenorrheic lady with gonadotropins with predictable response.

I wish you all the best.
I got good comments for my case discussion of HELLP syndrome, please continue to comment, it helps . I always welcome a good academic interaction through this news letter.

Sincerely Yours
Dr. D’Pankar Banerji

1. Options for Clomiphene citrate failure

1. Increasing the CC dose up to 250mg per day. In clinical experience, doses beyond 150 mg per day are rarely effective.
2. Metformin – of those patients who fail to respond to CC alone, if they are pretreated with metformin 500mg t.i.d. for 4-6 weeks prior to another course of CC, 90 % will ovulate.
3. Dexamethasone – 0.5 mg at bed time
4. Injectable gonadotropins

Oral hypoglycemic agents:

Insulin resistance is one of the major factors in PCOS. It may be due to defect in the insulin receptor or a post receptor defect. Insulin increases ovarian and adrenal androgen production, decreases the production of SHBG, and stimulates the pituitary secretion of LH. All of these lead to an androgenic milieu that interferes with the normal follicular development and ovulation. Any woman with ovulatory dysfunction and has symptoms of hyperandrogenism should be tested for serum androgens (DHEAS, 17-OH-P, Testosterone). Assessing fasting insulin level is not of much value, rather fasting plasma glucose and if needed 2 hour GTT should be done.

Patients with adult –onset diabetes mellitus have been treated effectively with oral hypoglycemic agents, such as metformin. Metformin improves the actions of insulin in several ways. It increases the uptake of glucose and reduces hepatic gluconeogensis. There are published data that have confirmed that metformin improves the insulin resistance in patients with PCOS, which results in a correction of the ovulatory dysfunction.

There are different views in the use of metformin in PCOS, but in a meta-analysis it was concluded that metformin improved the rate of ovulation. The ovulation rates were different between the metformin and placebo groups; 46 vs. 26%. The rates of ovulation in those who took metformin + CC and CC alone were 76 vs. 42%, respectively. While metformin may be effective by itself it may take up to 6 months to appreciate ovulatory cycles.
Metformin treatment may be considered in any patient with signs of PCOS. Check a fasting glucose and if the fasting blood glucose is greater than 100 mg/dl, perform a 2 –hour glucose tolerance test to rule out diabetes. Renal function and liver functions tests should be done prior to that. Lactic acidosis is more common in patients with renal or hepatic dysfunctions.

Doses of metformin: Initiate with 500 mg per day for seven days then in one tablet twice a day for one week and then one tablet three to four time a day. The medication should be taken with meals.
Long term treatment: It can be considered for up to 6-12 months. This is especially attractive treatment for obese women and for those women who want to avoid a multiple pregnancy associated with ovarian stimulation medications.

Short treatment: For those patients who want to move on quickly to treatment, a short course of metformin (4-6 weeks) can be used before moving on to CC. For those who failed to respond to CC alone, pretreatment with metformin many times will improve their response when CC is tried again.

2. Hypogonadotrophic Amenorrhea:

Presents as:

Young girls are with parents with complaints of no signs of puberty (secondary sexual characters).
Female partners with primary or secondary amenorrhea and with infertility.
This diagnosis is done by

1. No withdrawal bleeding after progestagen withdrawal
2. Bleeding after sequential estrogen and progestagen
3. Low FSH and LH levels
4. Transvaginal USG or TAS:  Small uterus with very thin endometrial lining, small ovaries without or with very small follicles (It helps to rule out pregnancy too in young girls!!!!)

This condition is characterized by a deficiency of pituitary or hypothalamic hormone secretion (particularly gonadotropins) it accounts for 40-50 % of all cases of amenorrhea. It is diagnosis of exclusion after pituitary tumors have been evaluated and ruled out. Hypothalamic amenorrhea may be secondary to stress, less than normal weight, or an eating disorder. Stress leads to an increased output of corticotrophin-releasing hormone, which subsequently results in decreased GnRh pulsatile secretion and thus decreased secretion if FSH and LH.

The resulting hypoestrogenism in these cases may lead to the development of osteoporosis.
Important influential factors include the critical level of body fat and stress. About 17% body fat is necessary for initiating the menarche and about 22 % of body fat is necessary for maintaining the menstrual regularity. Simply the body mass index a fair judgment of this fat storage. Body mass index of 17 or less are usually present with this complaint.

Anorexia nervosa, a condition characterized by extreme weight loss with no known organic cause, can affect adolescent development and results in amenorrhea.

Female athlete triad is a syndrome defined by amenorrhea, and eating disorder, and osteoporosis. Typically, this condition is seen in athletes whose performance is enhanced by a lean physique, such as long distance runners. The etiology most likely involves an inadequate caloric intake for the level of energy expended, which leads to hypoestrogenism and amenorrhea.

OVA1 should only be used to compliment other diagnostic and clinical procedures; the test is not indicated for screening purposes or to achieve a definite diagnosis of ovarian cancer.

3. Capsule on CA-125 Dr.Sarika Sharma MS (ObGy)

• CA 125 is a high molecular weight surface glycoprotein
• It is an antigenic determinant derived from coelomic epithelium and mullerian duct
• Its normal level is < 35 U / ml
• Mainly used to differentiate between a benign ovarian mass and a malignant epithelial ovarian mass
• It is elevated in 80% of patients with epithelial ovarian cancers particularly non mucinous tumours
• But unfortunately, this antigen is also detectable in a variety of benign conditions like fibroid, endometriosis, pregnancy, pelvic inflammatory disease, ectopic pregnancy, adenomyosis, ovarian cyst adenomas, liver disease, pancreatitis, peritonitis, renal failure, luteal phase of menstrual cycle and even in 1% of normal individuals!
• Serum CA 125 levels can be used during chemotherapy to follow these patients whose level were positive at the initiation of therapy. The change in level correlates with response
• the levels frequently become undetectable after the initial surgical resection and one or two cycles of chemotherapy
• Positive levels are useful in predicting the presence of disease, but negative levels are an insensitive determinant of the absence of disease
• The predictive value of the positive test was 100% during follow up
• But if the level was less than 35 U/ml during follow up, 44% of patients had disease at 2nd look surgery
• If levels are  persistently elevated after 3 cycles of chemotherapy, they most likely have resistant clones and if level rise after treatment, the disease has comeback and the treatment has failed

4. Fellowship course in Reproductive endocrinology and Infertility

Program :

DAY 1

THEORY :
Basic reproductive endocrinology of female, Understanding of Hypothalamo-pituitary-gonadal axis

PRACTICAL:
Microscopy, stereozoom, trinocular, micro-photography and documentation ,inverted microscope and micromanipulator introduction

DAY 2

THEORY
Introduction to cell biology and cell division and cell culture, Meiosis and Gametogenesis,  Culture media preparation

PRACTICAL:
Tissue culture media preparation for IUI

DAY 3

THEORY
Basic endocrinology of Male, Hormonal control of Spermatogenesis

PRACTICAL
Routine semen analysis, sperm preparation methods for IUI, hands on

DAY 4

THEORY
Anovulation and Polycystic ovaries ,Hirsutism

PRACTICAL
Preparation of culture dishes and droplet making under oil

DAY 5

THEORY
Amenorrhoea ,How to deal with it.

PRACTICAL
Hands-on retrieval of mammalian eggs and their in vitro maturation

DAY 6

THEORY
Induction of Ovulation for IUI and IVF

PRACTICAL
Observation and demonstration of Cryo preservation techniques

• Theory classes will be from  9.30am to 11.00am.
• Candidates can repeat their practical, if they wish
• Candidates will be involved in daily OPD infertility counseling and treatment approach from 11-4 . They will see and do transvaginal sonography (as patients allow).
• They will be allowed to observe IVF and ICSI procedures done during their stay. They will have access in embryology laboratory to see the lab set up and equipments and exposure to embryology ( observation), fertilization to blastocyst stage and embryo transfer.*
• Fees : Rs .25,000 per candidate. Students** : Rs.15,000
• One or Two  candidates are allowed in one batch
• Course will be from Monday to Saturday of a week.
• Certificate of attendance will be given at the end of the course
• Prior registration is must with full payment( demand draft in the name of Dr.D'Pankar Banerji,payable at Jabalpur)
• Stay and food is extra. Stay @ Rs. 500-1500/day can be arranged in nearby hotels within one kilometer of the venue

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

Venue : Ideal Fertility, ICSI,IVF and Genetic center, Jabalpur
Depending on the availability of cases.
Student, applies to undergraduate medical students and residents. A letter from the Head of the Department proving the participant’s student status must accompany each student registration

Sale :
CO2 Incubator Minicellmate, GenX USA , 6yrs old Rs. 1,00,000 ( working condition)
Logiq XP ,Color Doppler,2005 with three probes ( TV/TR, Abdominal Sector,and Linear) in excellent condition at Rs. 7,00,000( owner going for 4-D machine).