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Failing ovary
The document discusses premature ovarian insufficiency (POI), also known as premature ovarian failure. It provides information on: - The prevalence of POI is approximately 1% in the general population. - Common causes of POI include genetic factors like Turner syndrome, Fragile X syndrome, and other chromosomal abnormalities. - POI can be diagnosed based on menstrual irregularities, elevated follicle-stimulating hormone levels, and low estrogen levels. - Management of POI focuses on hormone replacement therapy, lifestyle changes, fertility preservation and treatment, and prevention of long-term health issues associated with low estrogen levels like osteoporosis.
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Failing ovary
- 1. FAILING OVARY DR SHIPRAKUNWAR MD,FICOG,FMAS,MRCOG(UK) PROFESSOR DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY ERA’S LUCKNOW MEDICAL COLLEGE
- 2.
- 3. At birth around1-2 million oocytes 6-7 million at 5 months Only 3 lac OVARIAN FOLLICULAR DEVELOPMENT 500
- 4. DNA, proteins, andmessenger RNA (mRNA) NO FURTHER PRODUCTION OF OOCYTE This time is utilised for Most oocytes are lost during fetal development, and the remaining follicles are steadily “used up” throughout the intervining years until menopause OVARIAN PHYSIOLOGY
- 5. Quantitative & Qualitativedecline of follicle pool
- 6. showed thatproduction of oocytes and corresponding folliculogenesis can occur well into adult life.
- 7. The reservoir ofgermline stem cells responsible for this oocyte development appears to reside in the bone marrow. Study in humans is awaited and the result of such study may provide the clinical leverage in disorders.
- 8. POOR OVARIAN RESERVE CLINICAL 1.Age 2. History of poor response or cancelled cycles 3. Menstrual cycle length BIOCHEMICAL AMH, inhibin B,FSH PROVOCATIVE TESTS CCCT ULTRASOUND MARKERS AFC,OVARIAN VOLUME
- 9. Premature ovarian insufficiency •Aging is associated in decline of ovarian function, however, if it occurs earlier than 40 years of age it is premature ovarian insufficiency ( premature ovarian failure )
- 10. STAGES OF PREMATUREOVARIAN INSUFFICIENCY Occult Biochemical Overt
- 11. Ovarian Clinical Situation Menses Gonadotropins Fertility Occult insufficiency NormalNormal Reduced Biochemical insufficiency Abnormal Elevated Reduced Overt insufficiency Abnormal/Abse nt Elevated Reduced/ABSENT
- 12. PREMATURE OVARIAN INSUFFICIENCY Apartfrom menstrual problems and infertility, POI is a serious endocrine disorder as it leads to a two fold age specific increase in mortality due to cardiovascular disease, stroke and osteoporosis.
- 13. Stud Coulam CB,et al. Obstet Gynecol. 1986. • Cohort of 1858 women born between 1928 and 1932. these women were followed for date and type of menopause. AGE No.OF WOMEN 15-29 YEARS 10/100 women year 30 - 39 76/100 women year 40- 44 881/100 women year 1 percent risk before 40 years
- 14. The prevalance is10-28 % in women presenting with primary amenorrhea, whereas in secondary amenorrhea the prevalance is 4-18%.
- 15. ETHINIC VARIATION ININCIDENCE 1.4 % African – American and Hispanic descent 1% Caucasian 0.5% Chinese 0.1% Japanese
- 16.
- 17. S No Causes 1Idiopathic 88.2% 2 X chromosome abnormalities Turner/Turnersyndrome-likekaryotype FMR- 1premutation(Xq27.3) Bone morphogenetic protein Other Xchromosome abnormalities (deletion, translocation, others 6.7% 3 Autosomal causes FSH receptor mutation Blepharophimosis ptosis epicanthus inversus syndrome 0.5% 4 XY Gonadal dysgenesis 1.6% 5 Iatrogenic hysterectomy Chemotherapy/radiotherapy Uterine artery embolisation 2.1%
- 18. S No Causes 7Infections ? 8 Cigarette smoking ? 9 Other Autoimmune diseases associated with POF are thyroid, parathyroid, diabetes mellitus, hypophysitis, chronic candidiasis, autoimmune haemolytic anaemia, SLE, Myasthenia Gravis and Crohn’s disease. 0.8%
- 19.
- 20. Not necessarily youwould find exact phenotypic features American Gymnast Missy Marlowe Dr. Catherine Ward Melver
- 21. Fragile X syndrome(X-LINKED DOMINANT) Developmental problems including learning disabilities and cognitive impairment. Males are more severely affected by this disorder than females. May also have anxiety and hyperactive behavior such as fidgeting or impulsive actions/ attention deficit disorder (ADD), which includes an impaired ability to maintain attention and difficulty focusing on specific tasks. Most males and about half of females with fragile X syndrome have characteristic physical features that become more apparent with age. These features include long and narrow face , large ears , a prominent jaw and forehead , unusually flexible fingers ,flat feet and in males, enlarged testicles
- 22. • INDUCED PREMATUREMENOPAUSE- Gonadal toxicity due to chemotherapy, especially with alkylating agents or with radiotherapy, leads to amenorrhea which is reversible if only the mature follicles are destroyed and irreversible when all the primordial follicles are destroyed. Complete ovarian failure occurs with a dose of 20 Gy of radiation. Surgical menopause is induced by oophorectomy.
- 23. hysterectomy maybeassociated with an early menopause due to damage to ovarian blood vessels, it may also be due to inflammation. Uterine Artery embolization interferes with ovarian blood supply.
- 24. Clinical Presentation • Menstrualirregularity • Primary ammenorhoea ( 20%) • Secondary ammenorhoea • Symptoms of oetrogen deficiency • hypothyroidism • Diabetes mellitus • hypoparathyroidism • Family history of POI • Mental retardation
- 25. Diagnosis and evaluation: Anyyoung woman with less than 9 menstrual cycles per year or missing more than three or more consecutive menstrual cycles should be evaluated. FSH >25 AMH TSH PRL
- 26. USG • confirm absenceof follicles, low ovarian volume and poor ovarian blood flow Chromosomal analysis • Should be carried out in all patients who present with primary amenorrhoea or early onset ovarian failure. Gonads must be removed if a Y chromosome or its part is present, because the risk of malignancy Autoimmune screening • Anti-adrenal and anti-thyroid antibodies should be done in all women who present with late onset ovarian failure
- 27. BMD • Bone MineralDensity should also be assessed at it leads to increased incidences of Osteoporosis. OVARIAN BIOPSY • is not indicated
- 28.
- 29. MANAGEMENT To reduce the psychological traumaon their emotional health To manage the consequent infertility To prevent the long term effects of oestrogen deficiency arising from ovarian failure
- 30. Daily intake of1000 mg of calcium and 800 IU of vitamin D Avoiding smoking and alcohol Reduction of caffeine intake Regular weight bearing exercises Maintaining an active Lifestyle
- 31. Fertility management: The chancesof spontaneous conception in women with POI is 5-10% . However, advances in assisted reproductive techniques (ART) are a boon to these women who desire a pregnancy. In patients with a minimal ovarian reserve, conventional ovulation induction with exogenous gonadotrophins can be tried. Success rates can be improved by pre- treatment with oestrogen, thus lowering FSH levels followed by ovulation induction. In women with a confirmed diagnosis of POF, oocyte donation remains the most elective form of therapy
- 32. Oocyte donation: Oocyte donationand embryo donation has provided hope the only realistic strategy for women with POI to achieve motherhood. A retrospective analysis in 2009 demonstrated its success of oocyte donation in women with POF and physiological menopause. IVF with donor oocytes confers the highest chance of successful pregnancy with a success rate of 40-50% per cycle.
- 33. Menopausal hormonal therapy: offered to all POI women alleviate the symptoms due to oestrogen deficiency and more importantly to prevent the development of osteoporosis and cardiovascular diseases. In adolescents, replacement therapy is required to help induce secondary sexual characteristics. Women with POI will typically require high doses of oestrogen. They do well with conjugated oestrogens in a dose of 0.625–1.25 mg or transdermal oestradiol 100 mcg a day or oral oestradiol in a dose of 1-2 mg per day.
- 34. This typically achievescirculating serum oestradiol levels of, approximately, 100 pg/mL, which is the average level found during a normal menstrual cycle. Progesterone supplementation is recommended as micronized progesterone 100-200 mg or medroxy progesterone acetate 5-10 mg per day for 12-14 days per cycle. Progesterone is added to oestrogen, at least for 12 days every month in order to protect the endometrium against development of endometrial hyperplasia. The transdermal route offers the advantage of avoiding the first pass hepatic metabolism and subsequent effects on clotting factors and triglycerides (PDF) Premature Ovarian Failure.
- 35. • GLOBAL CONSENSUSSTATEMENT ON MENOPAUSAL HORMONAL THERAPY FOR WOMEN WITH PREMATURE MENOPAUSE: MHT is the most effective treatment for vasomotor symptoms associated with menopause at any age. Systemic MHT is recommended at least until the average age of natural menopause. Estrogen as a single systemic agent is appropriate in women after hysterectomy but additional progestogen is required in the presence of uterus. MHT is elective and appropriate for the prevention of osteoporosis related fractures and standard oestrogen therapy alone in women of age <60 years may decrease the coronary heart disease.
- 36. Local low doseestrogen therapy is preferred for women whose symptoms are limited to vaginal dryness or dyspareunia. The dose and duration of MHT should be consistent with treatment goals and safety issues should be individualised. Current safety data does not support the use of MHT on breast cancer survivors
- 37. Strategies for fertilitypreservation in young cancer patients: • Embryo cryopreservation • Oocyte cryopreservation • Primordial follicle extraction with IVM • GnRH analogue therapy during chemotherapy GnRH agonists at least 7 days prior to chemotherapy and continuing every 28-30 days throughout the chemotherapy duration leads to interruption of FSH secretion • Ovarian tissue cryopreservation • Ovarian tissue transplantation- lateral ovarian transposition >1.5 cm above the iliac crest has been significantly associated with ovarian preservation.
- 39. 1.The overall prevalenceof POI is : A) 1% B) 2% C) 3% D) 4% E) 5%
- 40. 1.The overall prevalenceof POI is : A) 1% B) 2% C) 3% D) 4% E) 5% ANSWER :1%
- 41. 2.With regard toTurners Syndrome, which is true A. Women always present with primary ammenorrhoea B. Women have karyotype 47 XXX C. Women are always infertile D. The external genitalia are underdeveloped E. Women should be investigated for cardiac anomalies
- 42. 2.With regard toTurners Syndrome, which is true A. Women always present with primary ammenorrhoea B. Women have karyotype 47 XXX C. Women are always infertile D. The external genitalia are underdeveloped E. Women should be investigated cardiac anomalies ANSWER :E
- 43. 3.With regard toFragile X Syndrome which is correct: A. It has autosomal dominant inheritance B. It has autosomal recessive inheritance C. It is X-linked recessive inheritance D. It is X –linked dominant inheritance
- 44. 3.With regard toFragile X Syndrome which is correct: A. It has autosomal dominant inheritance B. It has autosomal recessive inheritance C. It is X-linked recessive inheritance D. It is X –linked dominant inheritance Ans D