Luteal Phase Defect--when to suspect & how best to combat such with Progesterone or other allied agents?

ABC of LPD.

When to suspect?  There are eight known causes where LPD can follow:- Such eight causes are -1) Hyperprolactinaemia, 2) polymenorrhoea.  In cases of polymenorrhoea   with less duration of follicular phase the granulosa cells don’t get enough time to get functional competency, 3) Poor function of leutin cells :-In  cases  with tonic rise of LH (in PCOS & in other cases where one suspects there is possibility of premature luteinization and resultant poor functioning of such immature leutin cells.4) adenomyosis,5)  endometriosis, 6) aged women,7)   thin women with less adipose tissue—therefore low leptin in serum. It is known that leptin in low level suppress GnRH pulse ->low LH in luteal phase.

8) All ART cases as follicular cells are destroyed during the process of ovum pick up. Part B: How to diagnose LPD -Clinical

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Part C:  Treatment Modalities

A)               Tr of LPD by HCG:- L Support Drug  type I  Dose:- After documentation of ovulation:- I HCG  is administered as 2000 i.u. on postovulatory days 3,7, 10 th days. Or 5000 i.u. on day 5 or day 9 post ovulatory. In non-IVF cycles still many prefers HCG rather than Progesterone as L Support. It can be used in IVF cycles too where OI is done by antagonists and Trigger is done by agonists. In such settings HCG can be used as LPD Tr. In such cases HCG is used as 1500 i.u. every 4^th day. But one cannot use this if serum E2 is > 2500 pigmy/ml in IUI cycles and if > 4000 pg/ml in IVF cycles, when there are too many follicles – in such cases it is better to avoid HCG as L Support as existing balance will be more in favour of E2 than Progesterone due to  presence of too  many follicles already have raised E2.

L Support Drug II:_-) Progesterone as L Support:-

Types of progesterones:- In LPD which progesterone to use ?    Type of   Kind of Progesterone 1:_-Dihydrogesterone is not commonly used (Nagori-pp.76).

    Kind of Progesterone 2:_-           Natural Progesterone:- Oral/ Vaginal/Inj.

Vaginal progesterone is best:- of which effervescent type is best effective.  The advantages of effervescent tab are greater bioavailability, more sty. Absorption, Lower dose required, Less irritation and discharge. The tab disintegrates in 7-10 minutes Twice daily dose will be all right. Absorption is by passive transport and also cell diffusion. Common, Serum concentration may be low but efficacy is much, Tab, Suppositories, Creams, ointments, Oil based solutions,

Type of    Progesterone 3:_-           Progesterone Gel:- 8% conc.  90 mg: Micronised P: It is micronised P, in emulsion system, which also contain water soluble polymer, Polycarbophil –having mucin like action, By Ovulation Induction.

Type of  Progesterone :-4   :_-GnRH Agonist as L Support:- This agent if administered in luteal Phase –it increases the LH surge  & it also stimulates the endometrium where there are receptors for GnRH Agonists. Agonists administered in luteal phase increases the HCG.LH E2 and P levels.

Kind of LPD in ART pregnancies:-

Post OPU(Ovum Pick Up) and associated   damage to granulosa cell occur which causes diminished progesterone production - leading to  sometimes breakthrough bleeding unless supp by exogenous progesterone . Additionally, also elevated levels of e2 post OPU leads to negative feedback to progesterone.

Dose in ART pregnancies:-Also imp is route of administration of progesterone - orally - not useful as it is highly metabolized during first pass metabolism and so not fit for luteal phase support in ART. Intramuscular or vaginal routes are the best methods Maintain on dose - 25-50 mg/day injections or 90-200 mg tad