luteal phase support, progesterone, assisted reproduction, invitro fertilization, ICSI, implantation failure, HCG, estrogen, early pregnancy, infertility

1. LUTEAL PHASE
SUPPORT IN
IVF/ICSI
BY
MAGDY ABDELRAHMAN MOHAMED
LECTURER OF OB/GYN SOHAG UNIV.
2018

2. Etiology of Luteal Phase Defect (LPD)
in ART Cycles
• Removal of large quantities of granulosa cells during
oocyte retrieval.
• HCG administration for final oocyte maturation in
stimulated IVF cycle could cause LPD by suppressing LH
production via short-loop feedback mechanism.
• Continued down-regulation by GnRHa

3. DOES THE PROTOCOL AFFECT???
• Both agonists & Antagonists protocols require
luteal phase support.
(Kahraman et al, 2010)

4. OPTIONS FOR LUTEAL SUPPORT
Luteal support may be given as:
•Progesterone.
• HCG.
• Estradiol valerate.
• GnRha for luteal support.
• Co treatment.

5. Progesterone
Oral Ingestion
• Oral progesterone is extensively metabolized and
has systemic side effects. There is reduced
bioavailability.
• Micronized progesterone formulations initially
used orally are now used vaginally

7. Intramuscular Injection
• It is the most reliable route to achieve desired
concentration of progesterone.
• Rapidly absorbed, peak level is reached in 8 H.
• Serum progesterone levels remain sustained
compared to other routes.

8. Intramuscular progesterone
• The doses of IM progesterone used for LPS vary
between 50 and 100 mg/day.

9. Vaginal progesterone
• Advantages of vaginal progesterone are patient
comfort and effectiveness.
• High uterine concentration with low serum
concentration.

10. Vaginal progesterone
• It does not cause drowsiness or sleepiness.
• Problem of vaginal discharge.

12. Gel form
• Progesterone gel administration is delivered
comfortably.
• There is no need to lie flat after insertion.
• The dose is 90 mg daily or B.D.

14. Rectal Administration
• This route of progesterone administration is not
widely accepted.
• Minimal clinical trials on t.his method

15. Timing of Luteal Support
• The timing of LPS should not be later than
day 3 after oocyte retrieval.
• The hCG administered for final oocyte
maturation covers the luteal phase for a
maximum of 8 days.

16. WHEN TO STOP
• Minimum 14 days from the day of ET until
the day of a positive HCG test (Andersen et al.,
2002).
• Minimum 18 days following OR (Mochtar et
al., 2006) .
• Progesterone supplementation in IVF
support early pregnancy through 7 w
(Andersen et al, 2002, Aboulghar et al, 2008).

17. OPTIONS FOR LUTEAL SUPPORT
Luteal support may be given as:
• Progesterone.
•HCG.
• Estradiol valerate.
• GnRha for luteal support.
• Co treatment.

18. HCG
• HCG is an indirect form of luteal support which
acts by stimulating corpora lutea to produce
progesterone.
• Dose 1500-2000 IU/day.

20. HCG
The disadvantage of using hCG:
• Increasing rates of OHSS.

21. HCG
Luteal support with hCG should be
avoided:
• E2 levels are >2,500 pg/ml on the day of
hCG administration
• The number of follicles is >10.

22. OPTIONS FOR LUTEAL SUPPORT
Luteal support may be given as:
• Progesterone.
• HCG.
•Estradiol valerate.
• GnRha for luteal support.
• Co treatment.

23. Estradiol
• The role of estradiol is not clear.
• There is a drop in estrogen concentration
in the luteal phase.

24. Estradiol
• The difference in pregnancy rates between two
regimens, i.e. progesterone only and
progesterone plus estrogen, is very small.

26. OPTIONS FOR LUTEAL SUPPORT
Luteal support may be given as:
• Progesterone.
• HCG.
• Estradiol valerate.
•GnRha for luteal support.
• Co treatment.

27. GnRh Agonist
• Support corpus luteum by stimulating secretion
of LH by the pituitary.
• Acting on endometrium by locally expressed
GnRh receptors.
• Direct effect on the embryos.

28. GnRh Agonist
• A single dose of GnRH agonist (0.5 mg leuprolide
acetate) administered subcutaneously on day 6
after ICSI in both agonist and antagonist cycles
enhanced pregnancy rates
• Oliveira JB 2010.

29. Results of the 2011 Cochrane
Database Systematic
• Oral route is associated with reduction in
pregnancy rates compared to
intramuscular or vaginal but was not
statistically significant.
• There is evidence of benefit of
intramuscular over vaginal route in terms
of outcome of ongoing pregnancy and live
birth rate.

30. Cont.
• There is no significant difference in pregnancy
rate between vaginal progesterone gel and other
types of vaginal progesterone.
• There was no significant difference between
progesterone and hCG or between progesterone
and progesterone plus hCG or oestrogen in
terms of pregnancy and miscarriage rates.

31. OPTIONS FOR LUTEAL SUPPORT
Luteal support may be given as:
• Progesterone.
• HCG.
• Estradiol valerate.
• GnRha for luteal support.
•Co treatment.

32. Co treatment
Ascorbic acid
• The addition of ascorbic acid provided no
additional benefit in stimulated IVF cycles,
regardless of dose used.
• Griesinger G et al 2002.

33. Steroids
• There is a hypothesis that immunosuppression by exogenous
steroids as a co-treatment for luteal phase support can be
used to improve rates of embryo implantation and pregnancy.
• No proven efficacy.

34. Aspirin
• Aspirin increases uterine blood flow; hence, it was
postulated that it would increase endometrial receptivity
& implantation.
• Controversial.

35. Sildenafil
• Sildenafil citrate improves the uterine
artery blood flow and the sonographic
endometrial Thickening.

36. Low molecular weight heparin
• Anticoagulant effect
• Modulates blastocyst apposition,
adherence and invasion
• May benefit but avoid routine use until
further research.
• Cochrane Review 2013.

37. Granulocyte colony stimulating Factor.
• Subcutaneous or intrauterine catheter.
• ? Interaction with immune system.
• Promising role.

38. Intravenous Immunoglobulin
• Reduces NK cell activity.
• Lack of evidence in APA negative women.

39. Atosiban
• Reduces uterine contractility?
• Priming of endometrium.
• Further studies required.

40. Neuromuscular Electrical Stimulation
(NMES) Therapy
• Pelvic floor NMES was found to
significantly enhance endometrial
thickness in patients with thin
endometrium.