Mild ovarian stimulation & IVF in women with poor ovarian response

1. Could mild IVF displace conventional IVF in poor responder women undergoing IVF/ICSI treatment cycles: Systematic review & meta-analysis
Youssef AFM.Mohamed
mohamedyoussef1973@gmail.com
Cairo University

2. Introduction
• ≈ 9-24% of IVF/ICSI patients respond
poorly to ovarian stimulation !!!
Poor ovarian responders

3. Natural & ART Populations

4. Different treatment options
Various Pituitary down regulation
protocols ??
+
High dose of Gonadotropins??

5. What is the problem ?
High doses of gonadotropins
• Low pregnancy rates.
• High Cost
• Embryos of lower quality.
• Moreover, Such a demanding protocol is more
burdensome to the patient
The patient pay more and get less
which is unfair

6. Mild ovarian stimulation
The administration of :-
• Low doses (fewer days) of exogenous Gonadotropins
in GnRH antagonist co-treated cycles,
• And/or oral com-pounds (like anti-estrogens, or
aromatase inhibitors) has been proposed to be an
alternative approach

7. Mild ovarian stimulation
1. Clomiphene citrate ± minimal dose of FSH/HMG ±
GnRH antagonist,
2. Letrozole ± minimal dose of FSH/HMG ± GnRH
antagonist
3. lower dose of FSH/HMG versus higher dose of
FSH/HMG.
4. Natural cycle/modified natural cycle ± minimal dose of
FSH/HMG ± GnRH antagonist.
5. GnRH antagonist versus long GnRH agonist,
6. GnRH antagonist versus short GnRH agonist

8. Aim of the review
• We conducted a systematic review & meta-analysis of
prospective randomized trials to evaluate the efficacy
of different modalities of mild stimulation in poor
ovarian responders
kasr al ainy school of Medicine
Cairo University

9. Inclusion criteria
• Type of studies: RCTs
• Participants: Infertile couples with poor ovarian
response undergoing IVF/ICSI
• Intervention: various mild ovarian stimulation modalities
and GnRH antagonist protocol versus long/ short GnRH
agonist protocol for pituitary downregulation
kasr al ainy school of Medicine
Cairo University

10. Outcomes
• Primary outcome: clinical pregnancy rate.
• Secondary outcomes:
1. Duration of stimulation,
2. Amount of FSH,
3. Number of retrieved oocytes,
4. Number of embryos transferred,
kasr al ainy school of Medicine
Cairo University

11. Literature search
• Menstrual Disorders & Subfertility Group's Specialised Register of
controlled trials
• The Cochrane Central Register of Controlled Trials (CENTRAL)
• MEDLINE (1966 to Jan 2012)
• EMBASE (1980 to Jan 2012)
• National Research Register
• Web-based trials databases such as Current Controlled Trials
• References check.
• We also contacted drug companies for any published, unpublished or
ongoing studies not identified with our search strategy
• No language restriction
kasr al ainy school of Medicine
Cairo University

12. Results

13. Flow diagram of study selection
kasr al ainy school of Medicine
Cairo University
Publications excluded, (n= 295)
RCTs included in meta-analysis (n=29)
RCTs withdrawn (n=0)
RCTs with usable information (n=29)
Potentially relevant publications identified and
screened for retrieval (n= 324)

14. CLINICAL PREGNANCY RATE
(CPR)

15. Ongoing pregnancy rate

17. CYCLE CANCELLATION RATE

20. DURATION OF OVARIAN
STIMULATION

23. AMOUNT OF
GONADOTROPINS

26. NO. FOLLICLES RETRIEVED

29. NO. EMBRYOS TRANSFERRED

32. Summary
There was no evidence of statistically significant difference
as regards the CPR between:-
• Letrozole-mild IVF group and control group
• CC-mild IVF group and control group
• Lower dose FSH/HMG versus higher dose FSH/HMG
• Natural/modified natural- IVF group and control group
• GnRH antagonist co-treated IVF versus long GnRH
agonist and GnRH antagonist co-treated IVF versus
short GnRH agonist

33. Studies characteristics
The overall methodological quality of the trials was:-
1. Good
2. Published as a full manuscript in peer-reviewed journals.
3. The studies were generally small and not well powered for all the
clinical relevant outcomes.
• Consistencies were found among the studies in outcomes such as
CPR & cancellation rate
• There were Inconsistencies between studies in outcomes such as
number of oocytes, duration of stimulation and amount of Gn used.

34. Studies characteristics
Although the inconsistency of studies ‘results in a
meta-analysis reduces the confidence of
recommendations about treatment, it is an
expected due to clinical and methodological
diversity between studies such as inclusion
criteria for participation and study quality but it
cannot be regarded as a major cause of the
differences in the results of the studies

35. Summary of results
The present meta-analysis indeed suggests that
various modalities of mild ovarian stimulation in
poor responders result in:-
1. ≈ Comparable pregnancy rates
2. ≈ Comparable number of retrieved follicles
3. ≈ Comparable cancellation rate
4. Shorter duration of stimulation
kasr al ainy school of Medicine
Cairo University

36. Take home message
• In view of its equivalence, mild ovarian
stimulation/ IVF could replace conventional
IVF protocols in women with poor ovarian
stimulation undergoing IVF/ICSI treatment
cycles
kasr al ainy school of Medicine
Cairo University

37. Results