LUTEAL PHASE SUPPORT IN ART
Dr. Jyoti Bhaskar
Director - LIFECARE IVF
Consultant – Pushpanjali Crosslay Hospital
∗ 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
∗ What is LPD?
∗ Why is luteal support required ?
∗ Who requires the support ?
∗ What are the options?
∗ Which route ?
∗ How much & how long ?
Inadequate Endometrial Maturation due to Qualitative
or Quantitative disorder in Corpus Luteum Function.
receptors in endometrium
Inadequate Secretion of
progesterone by Corpus luteum
Lpd --- diagnosis
PROBLEMATIC AND CONTROVERSIAL
No practical diagnostic method
has been validated
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
∗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
LPD -- Diagnosis
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
∗ 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
∗ 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
∗ Women with strenous exercises and underweight
Who require luteal support ?
∗ Supraphysiological estrogen levels may induce
∗ 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
Luteal Support : Drug ?
∗ Human Chorionic Gonadotropins
∗ GnRH agonist
It should be luteomimatic and not luteolytic
Micronized progesterone is the drug of choiceMicronized progesterone is the drug of choice
Oral Intramuscular Vaginal
Only 10 % absorbs
Not very effective.
First hepatic pass
Side effects like sedation &
P4 in oil base,
Reliable & consistent n
plasma level of P4
Rapidly absorb in 2-8 hrs.
P4 level maintain for > 72
Difficult & very painful inj
Local reaction & abscess.
Non compliance by pt.
Targeted organ delivery
High conc. In ut &
First uterine pass effect
Mini systemic side effect
Good Pt. compliance
Self administration, no
prick of needle
∗ High affinity for progesterone receptors
∗ Safe, well tolerated, non androgenic, less side effects
∗ Orally active at lower doses
Dose : 20 – 30 mg orally per day
When to start ?
∗ Not too early / not too late – both are detrimental
∗ Acceptable window 0f 24 – 48 hrs after oocyte retrieval /
∗ From the same day of IUI
dal preto et al , 2008 , fertil steril 2010 , fertil steril 2009
∗ 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
How long ?
- Not established firmly
- Often continued unnecessarily till 12 week
- Most evidence based studies suggest to continue till 9
Outcome of different studies remains
- Optimal route of administration has not been
- Equal number of studies support both vaginal &
- Recent Cochrane review concluded that no significant
difference between different routes.
∗ 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
∗ Most of the time, luteal cells are incompetent – HCG is
∗ 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)
Luteal phase support for assisted
∗ Significant effect in favor of Progesterone
∗ (Dydrogeston) fares better than micronized
∗ 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.
∗ Benefit from addition of GnRH agonist to
∗ 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,
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
Take home message
∗ No treatment for LPD has shown to improve
pregnancy rates in unstimulated, natural cycles
∗ Identify patients who require luteal phase
∗ ALL PATIENTS OF ART NEED LUTEAL SUPPORT
Take Home Message
∗ VAGINAL progesterone is equally
efficacious and better tolerated than
∗ Adequate dosage must be prescribed
to achieve better outcome
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