POF and Infertility !!

Dr Richa Sharma, Dr Amit Basnotra
Dear Readers, today we will discuss about a condition which can happen primarily and even secondarily in females who are planing for the second baby while they may have the first baby naturally and without any challenges while when they think of another pregnancy,it may be a challenge for them. Condition we will dicuss is – premature Ovarian Failure(POF).
What is POF?
Premature ovarian failure (POF) describes a syndrome consisting of more than 3 months amenorrhea, sex steroid deficiency and elevated levels of gonadotropins in a woman aged under 40 years at the onset of the amenorrhea
Incidence of POF:
It is estimated to affect approximately 1% of women under 40 years of age, 0.1% of women under 30 years of age, and 0.01% of women under 20 years of age
Types of POF:
Primary (spontaneous POF) or
Secondary (induced by radiation, chemotherapy or surgery)
What could be reason behind ?
Reason behind in most cases is unknown but grossly can be- -follicle depletion and follicle dysfunction
1. Ovarian follicle depletion
A. Low initial follicle number- Genetic reasons at level of Gonads, Thymus etc
B. Accelerated follicle atresia
a. X chromosome related (Turner syndrome, X chromosome deletions and translocations)
b. Fragile mental retardation 1 (FMR1) gene permutation
c. Specific gene abnormalities – Galactosemia
d. Iatrogenic
e. Environmental toxins
f. Idiopathic
g. Viral oophoritis (theoretical possibility that has not been proven)
h. Autoimmunity (theoretical possibility that has not been proven)
2. Ovarian follicle dysfunction
A. Steroidogenic enzyme defect
B. Specific genetic defects (blepharophimosis-epicanthus-ptosis syndrome)
C. Signal defects
D. Autoimmunity
E. Infection
F. Idiopathic (resistant ovary syndrome)
How it can impact the Fertility Potential of a Female ?
Women with POF are not necessarily sterile. Resumption of ovarian activity (be it intermittent) occurs in approximately 50% of these women. However, the chance of spontaneous conception is <5%,
What can be done?
In vitro fertilization involving oocyte donation provides individuals the greatest possibility of pregnancy as a normal uterus is present.
What All A Patient should know and be Aware ?
1. Inform patient abour POF and provide counselling, information and emotional support
2. Provide hormone replacement therapy/combined oral contraceptive pill up to 50 years of age and then yearly review as required
3. Provide calcium and vitamin supplements and encourage weight-bearing exercises
4. Provide contraception if required and advice on fertility issues
5. Monitor response to therapy and bone density according to individual requirements
6. Spontaneous remission can occur occasionally
7. There is no prospectively proven treatment to restore ovulation
8. Adoption or a change in life plans may resolve infertility for some couples
9. Ovum donation is an option for couples who desire to conceive
10. Follow-up and vigilance to identify few patients who will subsequently develop other components of the autoimmune polyglandular syndrome or non-organ-specific autoimmunity is important
11. In the absence of good long-term randomized prospective data, treatment should be individualized according to choice and risk factors
Case Report
To make it more easy to understand we will conclude it with an example in a simplified manner as how it can be presented and managed
A 25 year old woman ABC , first consulted with a background history of Primary Infertility for 3 years with irregular cycles and history of chronic thyroiditis with elevated FSH levels over the past 2 years ranged from 21.66 to 77.10 IU/ml. On a transvaginal baseline scan, uterus was smaller than normal in size with bilateral small ovaries . No follicles were visualized in both ovaries. . Husband’s semen analysis was however found to be normal.
In view of premature ovarian failure and her desire to conceive, patient was counseled for IVF with oocyte donation
Conclusion
Young women with POF have unique needs that require special attention especially when they are planning family.So treatment and counseling both needs to be individualized empathetically.
There is an urgent need to determine the scale of the problem, particularly after iatrogenically induced menopause, and to develop evidence-based guidelines based on solid research in order to optimize the care of this group of women.
The advances in the technology of cryopreserved ovarian tissue transplantation and in-vitro maturation of oocytes derived from stem cells may make it possible for some women with POF to use their own eggs for in-vitro fertilization.
Specific therapy for autoimmune POF-which could include highly specific blocking antibodies that would potentially prevent the follicular dysfunction and loss and avoid the adverse systemic effects associated with corticosteroids and other immunomodulatory therapies-will be possible in the future.
(The authors are Senior IVF Consultant and Senior Gastrentrologist)

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