1. LUTEAL PHASE SUPPORT IN ART
-- REVISITED
Dr. Jyoti Bhaskar
MD MRCOG
Director - LIFECARE IVF
Consultant – Pushpanjali Crosslay Hospital
Lifecare Centre

2. ∗ LPD - 5 - 10 %
∗ Unexplained infertility - 15- 20 %
∗ A large fraction of unexplained infertility may be
because of LPD which is difficult to diagnose
∗ Recurrent pregnancy loss – 8 -12 %
∗ 40% of women with recurrent pregnancy loss may
be having LPD
HARD FACTS

3. ∗ What is LPD?
∗ Why is luteal support required ?
∗ Who requires the support ?
∗ What are the options?
∗ Which route ?
∗ How much & how long ?
OVERVIEW

4. Inadequate Endometrial Maturation due to Qualitative
or Quantitative disorder in Corpus Luteum Function.
LPD ------DEFINITION
Decreased progesterone
receptors in endometrium
Inadequate Secretion of
progesterone by Corpus luteum

5. Inadequate Luteal
Phase
Follicular Phase Secretory Phase
Inadequate FSH
secretion
Abnormal Gonadotrophin
pulses
Defective Folliculogenesis
Inadequate Estrogen
Insufficient endometrial priming
by estrogen
Poor mid cycle
LH surge
Hyperprolactinemia
Inadequate LH
secretion
Inadequate
Progesterone
receptors
Defects in CL
Decreased Progesterone
synthesis
Poor Secretory response

6. Lpd --- diagnosis
PROBLEMATIC AND CONTROVERSIAL
as
No practical diagnostic method
has been validated

7. LPD -- Diagnosis
When the luteal phase is shorter than 12 days, it is usually treated
BBT is a poor indicator of the quality of luteal phase and is therefore not an
adequate diagnostic tool.
Midluteal progesterone level of less than 10 ng/mL was considered
to be abnormal, the probability of falsely diagnosing LPD was as low
as 4%

8. SONOGRAPHIC CRITERIA
∗Rupture of follicle < 17 mm
∗Poorly formed or ill defined dominant follicle
∗Luteinised unruptured follicle
∗Lutein cyst formation
∗Absence of corpus luteum
∗Lack of endometrial echogenicity on 7th
postovulatory day
LPD -- Diagnosis

9.  Endometrial biopsy ---- was GOLD STANDARD
It is imprecise, invasive, not reproducible
LPD -- Diagnosis
Currently there is no reproducible, physiologically
relevant and practically clinical standard test to
diagnose LPD

10. Treatment
∗ Correction of underlying causes
∗ Emperical – supplemental progesterone, HCG or
ovulation Induction with CC or gonadotrophins
Ovulation induction strategies improve fertility by
inducing multiple ovulation and not correcting LPD

11. ∗ Confirmed cases of luteal phase defect
∗ Unexplained infertility
∗ Advanced reproductive age
∗ ART techniques – IUI / IVF / ICSI
∗ Hyper- prolactinaemia
∗ All down regulated cycles
∗ Recurrent pregnancy loss
∗ PCOS
∗ Women with strenous exercises and underweight
Who require luteal support ?

12. ∗ Supraphysiological estrogen levels may induce
premature luteolysis
∗ Follicular phase downregulation may impair luteal
phase LH release
∗ Pure FSH protocols lead to low LH values
∗ OPU causes granulosa cell disruption
∗ COH accelerates endometrial maturation
∗ To overcome any LPD if present
Why in ART Cycles

13. Luteal Support : Drug ?
∗ PROGESTERONE
∗ Human Chorionic Gonadotropins
∗ Estrogen
∗ GnRH agonist

14. It should be luteomimatic and not luteolytic
Micronized progesterone is the drug of choiceMicronized progesterone is the drug of choice
Ideal Drug

15. Progesterone Supplementation

17. Various routes
Oral Intramuscular Vaginal
Easy route
Micronized form
Only 10 % absorbs
Not very effective.
First hepatic pass
Side effects like sedation &
hypnosis
P4 in oil base,
Reliable & consistent n
plasma level of P4
Rapidly absorb in 2-8 hrs.
P4 level maintain for > 72
hrs.
Difficult & very painful inj
Local reaction & abscess.
Non compliance by pt.
Targeted organ delivery
High conc. In ut &
endometrium
First uterine pass effect
Mini systemic side effect
Good Pt. compliance
Self administration, no
prick of needle

19. ∗ Immunomodulator
∗ High affinity for progesterone receptors
∗ Safe, well tolerated, non androgenic, less side effects
∗ Orally active at lower doses
Oral Dydrogesterone
Dose : 20 – 30 mg orally per day

20. When to start ?
∗ Not too early / not too late – both are detrimental
∗ Acceptable window 0f 24 – 48 hrs after oocyte retrieval /
release
∗ From the same day of IUI
dal preto et al , 2008 , fertil steril 2010 , fertil steril 2009

21. How much?
∗ 300-600 mg / day seen to provide same effect as with
90 mg of vaginal gel
∗ Vaginal Progesterone yields lower serum
concentration but endometrial concentration is 30
fold greater than intramuscular.
(Fert. Steril 1994)
Most studies demonstrated equal efficacy involving
600 mg micronized vaginal progesterone

22. How long ?
- Not established firmly
- Often continued unnecessarily till 12 week
- Most evidence based studies suggest to continue till 9
weeks gestation

23. Outcome of different studies remains
controversial
- Optimal route of administration has not been
established
- Equal number of studies support both vaginal &
intramuscular route
- Recent Cochrane review concluded that no significant
difference between different routes.

24. ∗ Exact mechanism not known
∗ Single dose of 0.5 mg S/C on 6 th day after ICSI
∗ Increases implantation rate, CPR per transfer,
increases live birth rate
Single dose GnRH agonist
Addition of GnRH agonist to progesterone improved
outcome of live birth, clinical pregnancy and ongoing
pregnancy -- Cochrane 2011

25. ∗ Most of the time, luteal cells are incompetent – HCG is
not effective
∗ HCG supplementation is effective when specific
defect of post ovulatory secretion of LH exists
Why HCG is not an ideal choice?
10,000 iu for ovulation and then 2500 u every 3-4 days
HCG associated with higher risk of OHSS – Avoid it
( Cochrane 2011)

26. Luteal phase support for assisted
reproduction cycles
COCHRANE 2011
∗ Significant effect in favor of Progesterone
∗ (Dydrogeston) fares better than micronized
progesterone
∗ No evidence favouring a specific route or duration of
administration of progesterone.
∗ HCG, or hCG plus progesterone, was associated with
a higher risk of OHSS. The use of hCG should
therefore be avoided.

27. ∗ Benefit from addition of GnRH agonist to
progesterone
∗ Overall, the addition of other substances such as
estrogen or hCG did not seem to improve outcomes
Progesterone seems to be the best option
as luteal phase support,

28. Take Home Message
∗ Abnormal Luteal Phase may occur due to
medical conditions – Thyroid and prolactin
disorders . Infertile women should be
investigated and treated appropriately.
∗ No diagnostic test for luteal Phase
insufficiency has been proven to be reliable

29. Take home message
∗ No treatment for LPD has shown to improve
pregnancy rates in unstimulated, natural cycles
∗ Identify patients who require luteal phase
support.
∗ ALL PATIENTS OF ART NEED LUTEAL SUPPORT

30. Take Home Message
∗ VAGINAL progesterone is equally
efficacious and better tolerated than
I.M. preparations
∗ Adequate dosage must be prescribed
to achieve better outcome

31. ADDRESS
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