Ovarian reserve refers to the reproductive potential left within a woman's two ovaries based on number and quality of eggs. Diminished ovarian reserve is the loss of normal reproductive potential in the ovaries due to a lower count or quality of the remaining eggs

1. Dr. Laxmi Shrikhande
MD; FICOG ;FICMU
• Director-Shrikhande Fertility Clinic, Nagpur
• President Menopause Society, Nagpur
• National Corresponding Editor-The Journal of Obstetrics & Gynecology of India
• Senior Vice President FOGSI 2012
• Vice Chairperson ICOG
• Governing Council member ICOG 2012-2017
• Governing Council Member ISAR 2014-2019
• Governing Council Member IAGE for 3 terms
• Patron-Vidarbha Chapter ISOPARB
• Chairperson-HIV/AIDS Committee, FOGSI (2007-09)
• Received Best Committee Award of FOGSI
• Received Bharat excellence Award for women’s health
• President Nagpur OB/GY Society 2005-06
• Associate member of RCOG
• Member of European Society of Human Reproduction
• Visited 96 FOGSI Societies as invited faculty
• Delivered 3 orations
• Publications-Thirteen National & seven International
• Presented Papers in FIGO, AICOG, SAFOG, AICC-RCOG conferences
• Conducted adolescent health programme for more than 15,000 adolescent girls

2. Treatment of Decreased
Ovarian reserve
Dr Laxmi Shrikhande
Chief Consultant | Shrikhande fertility Clinic
Nagpur [Maharashtra] INDIA

3. Decline in Ovarian reserve
• Age related decline in female fertility well
recognised
– Starts at 30,
– rapid decline after 37,
– virtually zero at 43.
• Due to decrease in
– Oocyte quantity
– Oocyte quality

4. Ovarian Reserve

5. Why we need markers of ovarian reserve ?
• Age of onset of decline in ovarian reserve is highly
variable
• Hence, the need for a marker to predict ovarian
reserve and fertility potential
• To identify young women with diminished ovarian
reserve
• To identify women with adequate OR even at the
age where natural fertility is lost (41 yrs)

6. Ovarian reserve tests

7. • women over 30 years of age
• women with a history of exposure to a confirmed
gonadotoxin, i.e., tobacco smoke, chemotherapy,
radiation therapy.
• women with a strong family history of early menopause
or premature ovarian failure.
• women who have had extensive ovarian surgery, i.e.,
cystectomy and unilateral oophorectomy.
Whom to subject for marker tests ?

8. Clinical application of OR test
• In general the average age at first child is 30 yrs
• Accurate OR testing will motivate some women to
start family early or go for oocyte frezing
• Alternatively it can reassure some women about
delaying childbirth
• Helps in individualisation of treatment plan-expectant
to ART

9. But we want
a baby !
Ovarian reserve markers helps
Helps counsel the patient in advance so that patients can
make an appropriate and informed choice.
Individualize expectation of oocyte yield
Cost of drug regimens
Discomfort to the patient expected
Risk of complications
Chances of disappointment

10. summary
• ORTs till date have modest predictive value for
pregnancy outcome as this is dependent on many
more factors apart from OR
• ORTs are indicative of ovarian reserve status in both
the quantitative and qualitative sense
• ORTs at best should be considered as screening
tests and not as diagnostic tests
• Treatment should not be denied based on these
tests to assumed ovarian aged woman

11. Conclusion
• Anti mullerian hormone(AMH) alone or better in
combination with antral follicular count (AFC) is
a better indicator of ovarian reserve than any
other hormonal or sonographic markers available
at present.
• Also a good predictor of response to ovulation
induction both poor as well as excessive
response.

12. Treatment for Women with Diminished Ovarian
Reserve
• If no other cause, active treatment of unexplained
infertility
• Lipiodol
• Stimulated IUI
• IVF
• IVF with low ovarian reserve
• Fewer eggs
• Maybe none of ‘good quality’ in any cycle
• Younger age may compensate
• Does low ovarian reserve ↓ chance of success?
• Adjuvant treatments for poor responders

13. LH
• Rationale
• ‘Two cell – two gonadotrophin’ theory
• LH provides granulosa cells with androgen
precursors for estradiol biosynthesis by FSH
• Resumption of meiosis
• Progesterone production
• Evidence
• Mochtar et al (2010)
• Unconvincing for routine use
• Significant benefit in poor responders

14. Growth Hormone
• Rationale
• Regulates the effect of FSH on granulosa cells through ↑ IGF-1
• Roles in ovarian function include follicular development,
estrogen synthesis and oocyte maturation
• Evidence
• Duffy et al (2010)
• Unconvincing for routine use
• Significant benefit in poor responders
• LIGHT Study
• Will add to evidence base

15. The value of growth hormone supplements in ART for poor
ovarian responders.
• Recently, three meta-analyses have concluded that cotreatment with
GH improves assisted reproduction outcome in poor controlled ovarian
stimulation responders. Although generally GH supplements did not
increase controlled ovarian stimulation response or number of oocytes,
the supplements improved pregnancy and live-birth rates-thus speaking
for an effect on oocyte quality.
de Ziegler D Fertil Steril. 2011.
• DOSE; GH daily subcutaneous injection of 4 mg from day 21 of
preceding cycle along with GnRHa, until the day of hCG.
• Usually, 4 to 12 IU GH are administered s.c.,
• commencing on the day of ovarian stimulation with gonadotrophins.

16. Role of Androgen in follicular growth
• Androgens influence follicular growth in following ways :
1. Acts as a metabolic precursors for steroid production
2. Serving as ligands for androgen receptors
3. Promote follicle recruitment
4. Increases insulin like growth factor (IGF-1) in the ovary.
• This leads to improved follicular survival, increased follicle
numbers and higher E2 levels during stimulation.
• Androgens also suppress apoptosis, hence better oocyte and
embryo number as well as overall improved quality in the cohort
of embryos produced.

17. Androgens
• Rationale
• ↑ IGF-1 resulting in positive effect on follicular
maturation and oocyte quality
• Stimulation of intra-ovarian androgen receptors
which stimulates release of IGF-1 thus promoting
follicle development
• Improved egg quality through growth hormone axis
• Regulation of LH-stimulated androgen and estrogen
production from follicles and ↑ expression of FSH
receptor resulting in ↑ no pre-antral and small
antral follicles
• Promotes DNA repair in oocytes
• Benefits mitochondrial function in follicular cells and
oocytes
• Evidence
• DHEA ‘well
promoted’
• Testosterone
patches
• Nagels et al
(final stage of
peer review,
2015) – all
small studies

18. DHEA
• Reasonable assumption is that DHEA is an essential substrate for
steroidogenesis
• DHEA abnormally low
Lack of substrate for the production of Androstenedione, Testosterone, E2
Low concentration of these hormones

19. DHEA supplementation
• Investigated 120 women with diminished ovarian
reserve. DHEA 25mg was supplemented thrice
daily from 30 to 120 days.
• AMH concentration significantly improved after
DHEA (p=0.002)
• Women under 38 years demonstrated better
response.
• Gleicher et al Reprod Online 2010 Sept 21(3)
19

20. DHEA supplementation in IVF
• Women needing IVF experienced 23.6% clinical
pregnancy rate
• Those who showed an improvement in AMH levels
did better
• DHEA group also showed reduced miscarriage rates
• Reprod Bio Endocrinol 2009 Oct
20

21. Comparison between DHEA treated Patients and National Average
for Miscarriage

22. Addition of DHEA for poor responder Prospective
Randomised study
• Thirty three patients underwent 51 IVF cycles (17 DHEA
&16 control)
• All patients underwent Long Protocol IVF.
• Wiser et al: Human Reproduction 2010

23. OBSERVATIONS
• DHEA group demonstrated a non significant increase in the
estradiol levels on day of hCG. (p=0.09)
• Improved embryo quality (p=0.04) between two cycles.
• DHEA group also has significantly higher live birth
rates.(23.1% v/s 4.0%) (p=0.05).
• Wiser et al: Human Reproduction 2010

24. Previously Reported Reproductive Benefits of DHEA
▪ Improves egg/embryo numbers
▪ Improves egg/embryo quality
▪ Improves spontaneous pregnancy rates
▪ Improves IVF pregnancy rates
▪ Improves time to conception
▪ Improves cumulative pregnancy rates
Casson et al. Hum Reprod 2000
Barad and Gleicher, Hum Reprod 2006
Barad and Gleicher, Fertil Steril 2005
Barad et al, J Assist Reprod Genet 2007

25. SIDE EFFECTS OF DHEA
• Minimal in doses upto 75-100 mg
• Acne, facial hair growth
• Deepening of voice
•

26. Conclusions
• Knowledge of low ovarian reserve can help to ‘change’
the approach
• Treat ‘unexplained’ with greater intensity
• Adjuvants in IVF for women with low response
• Transdermal testosterone (OR 2.6, 95%CI 1.3-5.2) or DHEA (OR
2.0, 95% 1.8-3.6)
• LH addition (OR 1.9, 95%CI 1.1-3.1)
• Growth hormone (OR 3.3, 95%CI 1.7-6.2)
• Egg donation is effective, but it is not the only option
and should be used ‘last line’

27. My World of
sharing happiness!
Shrikhande Fertility Clinic
Ph- 91 8805577600
shrikhandedrlaxmi@gmail.com