Tenement of Clomiphene failure

One of my x PG sent a WhatsApp message stating as “30 yr old woman,  trying time 7 months , PCOS. hormonal profile normal , HSA –Normal , ovulation induction done by  100 mg enclomiphene- 2 such cycles . No conception, in spite of Follicular monitoring . What is the next practical approach? “

My reply:- A) May try for  combined CC & hMG :For instance to  initiate  CC (50 or 100mg) from day 2 or 3 for 5 days. To commence Gonadotrophins (u-FSH or r-FSH) 50-75 IU on the last day of CC or a day after the last dose of CC, daily and see for response after 3-4 days. gradually step up GT dose, or remain same and reassess, hCG trigger can be given when lead follicle is beyond 18mm.

 Without provision of FM one cant or should not try from Gonadotrophins more so if facilities of E 2 estimation is available (preferably at some subsidy). His CC & G cycle becomes more relevant if only CC cycles had thin ET .

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But many of us have switched over to  enclomiphene as she did .. But  simple Clomiphene which is Zu+En is equally effective, What she didn’t mention in WhatsApp that  1) what was her Wt & BMI and counselling about   address weight management:- 2ollicles seen recruited,

3)  One can go by chronic low dose step up protocol as well in "non-responders".- In chr. low dose step up, one should  start with daily injection of GT at 37.5 IU only, say up to 7 or even 10 days. See for response and either increment slowly or keep the same. hCG at+18mm. Adding C C to GT reduces cost. May use Use R-FSH instead of HMG in PCOS cases with high LH: - on day 7/day 8: To cut cost one can start clomiphene 100 for 5 days followed by FSH from 7 th day onwards. Therefore to prescribe 100 mg cc from day 2 to day 6. Then inj FSH 75 iu on day 7, 8, 9. Day 13 of cycle today. Still MSF in both ovaries! Since she is pcos, high LH may be there so check levels 1st n recombinant fsh gives good results .Yes. Fir same reason gave her fsh and not fsh lh. If she has not responded to what I wrote above, do I need to do start her only on rFSH?  From day 2

 First I think a) one should try 2-3 cycles of CC & gonadotropins) . --> c) Gonadotrophins . iui + oi. To buy little time and give them enough time as trying time is less.

5)  Resort to LOD as a lost and last option. It may utmost decrease the OHSS severity in case of IVF. Indication of LOD:--To carry out  FSH AND LH on day 2 , if LH >2 times fsh , counsel pt for drilling , if pt not willing one  can try with 150 mg cc , may have god result .) .b) followed by drilling (if LH is high and PCO morphology is more echogenic stroma after proper counselling  

6) Metformin as  add-on

7) Inositol, once upon a time they were classified in the B-Complex group of vitamins and still considered a nutritional adjuvant, mostly from plants. Mode of action is not very clear, but helps to control hunger "center" as well. Many scientists still  don’t consider  it  as a "drug" for PCOS, but as any "vitamin-like adjuvant.

8) Vit D is an "in-vogue" drug. No harm giving in moderate dose, though Hypervitaminosis is known at a very high dose ..

 (9) Chr. Low dose: 10)) Use Letrozole in mid cycle instead of HMG: - I have seen some big centres stopping FSH temporarily giving letrozole 5 tablets in one and half day and then continuing FSH stimulation once they see a dominant follicle, 

Hypothalamic-PIT diseases are rare possibility. DHEASO4 for establishing Adrenal androgen excess and planning for corticosteroid Ry. Similarly review of semen other reputed Lab /PCT under your control may be thought of.