This document discusses luteal phase support in IVF. It explains that ovarian stimulation and follicular aspiration in IVF can compromise the corpus luteum, leading to luteal phase deficiency. Various medications are used for luteal phase support, including progesterone, HCG, estrogen, LH, GnRH agonists, aspirin, heparin, prednisolone, and sildenafil. Progesterone supplementation is considered mandatory for luteal phase support, while HCG is not recommended due to risk of OHSS. Estrogen may be used with progesterone. The role of other supplements like GnRH agonists requires more research. Luteal phase support is typically continued until a heartbeat is detected, around 6-

2. Luteal Phase Support in
IVF
Dr Kaberi Banerjee
New Delhi

3. Luteal phase
• Period between
ovulation and
establishment of a
pregnancy or onset of
menses

4. Pathophysiology - LPD in IVF
• Follicular aspiration for
oocyte

Aspiration and
mechanically disruption
of granulosa cells

Compromised corpus
luteum

5. Pathophysiology - LPD in IVF
• Multifollicular development

Supra- physiological
concentrations of steroids
secreted by high no. of
corpora lutea during early
luteal phase

Directly inhibiting LH
release via negative
feedback actions at HP
axis level

6. LPD – IVF Protocols
• Luteal phase - abnormal
• Cycle with GnRH agonists
• Prolonged suppression of pituitary LH secretion (3 weeks
after down regulation)
• Luteal phase inadequacy
• Cycle with GnRH antagonists
• Recovery of LH production from pituitary quite rapid
following cessation
• Still have significant reductions in pregnancy rates

7. Luteal phase support (LPS) in IVF
• Administration of
medications to support
the process of
implantation
• Saves the corpus
luteum
• Supplementation of
corpus luteum products

8. LPS in IVF
• Progesterone
• HCG
• Estrogen
• Luteinizing hormone
• GnRH Agonist
• Aspirin
• Heparin
• Prednisolone
• Sildenafil

10. Progesterone
Principle
LPD due to IVF
stimulation

Defective corpus
luteum

Progesterone levels

11. Progesterone
MOA
• Support corpus luteum
• Acts directly on
endometrium
(secretory
transformation of the
endometrium for
implantation and early
development of
fertilized ovum)

12. Progesterone
• Two groups
• Natural progesterone
(Micronized
progesterone)
• Synthetic preparations
(17-OHprogesterone
derivatives,
Dydrogesterone)

13. Progesterone - Forms
• Vaginal Micronized
• Oil based Intramuscular
• Vaginal Gel ( Crinone)
• Vaginal Ring ( Milprosa)
• Subcutaneous Lyophilized ( Prolutex)
• Progesterone Inserts ( Endometrin)
• Progesterone Spray

14. Progesterone - Dose
• Orally
• Very low level in blood
• Bioavailability < 10%
• Very high transformational dose
• Micronised progesterone (600 mg/day) & Dydrogesterone (20 mg/d)
• Inactivated by hepatic metabolism
• Vaginally
• Low level in blood but still causing endometrium transformation (400
to 600 mg/day)
• Directly distributed from vagina to uterus (first uterine pass effect)
• Intramuscular
• Very high level in blood (2 hours) but low in endometrium (50 to 100
mg/day)
• Uncomfortable because of pain
• Rectally
• No prospective randomized trails to compare with other routes

15. Progesterone - Doses
• Vaginal Micronized – 300-600mg
• Oil based Intramuscular - 50-100mg
• Vaginal Gel ( Crinone)- 90mg
• Progesterone Inserts ( Endometrin) -100mg
• Spray – 50 ml

16. HCG
Principle
LPD due to IVF
stimulation

Defective corpus
luteum

HCG levels

17. HCG
MOA
• Stimulates the ovaries (or
corpora lutea)

Boost production of
endogenous
progesterone & estradiol

18. HCG - Dose
• Intramuscular/Subcutaneous
• Low-dose hCG (1500 IU)

19. Estrogen
Principle
LPD due to IVF
stimulation

Defective corpus
luteum

Estrogen levels

20. Estrogen
MOA
• Support corpus luteum
• Acts directly on
endometrium
• Role - Still debatable

21. Estrogen - Dose
• Orally/ Vaginally
• 2 to 10 mg /day in divided
doses

22. Progesterone, HCG, Estrogen
Studies

23. Estrogen studies

24. Estrogen Studies

25. Luteinizing Hormone
Principle
LPD due to IVF
stimulation

 LH levels

26. Luteinizing Hormone
MOA
• Support corpus luteum
•  Progesterone
secretion

27. Luteinizing Hormone - Dose
• Subcutaneous injection
• 75 IU rLH (4 doses
every 3 days starting on
the day of embryo
transfer)

28. LH Study

29. LH Study

30. GnRH Agonist
Principle
LPD due to IVF
stimulation

 LH levels

31. GnRH Agonist
MOA
• Support corpus luteum by
stimulating secretion of LH by
pituitary gonadotroph cells
• Acts directly on endometrium
through locally expressed
GnRH receptors
• Acts directly on embryo

32. GnRH Agonist - Dose
• Single injection - 0.1 mg
Inj triptorelin
subcutaneously on Day
6 after ICSI
OR
• Three doses - 1 mg Inj
Lupride subcutaneously
on 6th, 7th and 8th after
oocyte retrival

34. Aspirin
MOA
• Inhibits enzyme cyclo-
oxygenase in platelets,
preventing thromboxane
A2 synthesis (potent
vasoconstrictor and
platelet aggregation
enhancer)
• Increase uterine and
ovarian blood flow and
tissue perfusion

35. Aspirin - Dose
• Orally
• 75 - 100 mg once daily

36. Aspirin Study

37. Heparin
MOA
• Anticoagulant
• Immunomodulatory
• Anti-inflammatory
effect
• Results in adhesion
of blastocyst to
endometrial
epithelium and
subsequent invasion

38. Heparin - Dose
• Subcutaneously
• Heparin 5000 IU every
alternate day
or
• Enoxaparin (LMWH)
40 mg daily/ every
alternate day

39. Heparin Study

40. Heparin Study

41. Prednisolone
MOA
• Immunosuppression
•  uterine NK cells
•  Cytokines
•  Endometrial inflammation

Better implantation rate

42. Prednisolone - Dose
• Orally
• 10 mg once daily

43. Prednisolone Study

44. Sildenafil
MOA
• Selective inhibitor of the
type V cGMP- specific
phosphodiesterase

Vasodilatory effects of
nitric oxide

Uterine blood flow

Improved endometrial
thickness

45. Sildenafil - Dose
• Vaginally
• 25 -75 mg once in night

46. Sildenafil Study

47. Onset of LPS

48. Onset of LPS

49. Duration of LPS
Most studies till heart beat confirmation
Common practice till 12 weeks.

50. No evidence of benefit in estimating
serum progesterone levels.

51. Luteal Phase-GnRH Agonist
Trigger

52. Luteal Phase – Frozen and
Recepient Cycles

53. Conclusion
• Ovarian stimulation (IVF) destroys
luteal phase function
• Hormonal levels
• Endometrium behaviour
• Luteal phase supplementation-
• Progesterone supplementation mandatory
• Vaginal/IM
• 300-600mg vaginal/100mg IM
• Egg pick up- heart beat
• No need of estimating serum levels.

54. Conclusion
• Luteal phase supplementation-
• HCG causes OHSS risk (Should not be used)
• Estrogen – Should be used with
Progesterone
• Role of GnRH agonist – Controversial
(More studies required)
• Role of heparin and prednisolone in
recurrent ivf failure or recurrent abortions
• Role of Sildenafil in thin endometrial
thickness
• No role of luteinising hormone, aspirin,
ascorbic acid