I do not use antagonists in high responders (e.g., PCOS) because it interferes with the assay of E2 (often causing the value to be understated), a valuable index in assessing risk for the development of severe/critical OHSS. I also do not believe in the agonist trigger to prevent OHSS. The reason is that the magnitude of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the oocyte aneuploidy index.

 

Down-regulation + “prolonged Coasting: My approach is consistently to use a long pituitary DR protocol with an agonist, coming off 1-2 months on the BCP. The latter is intended to lower LH and thereby reduce stromal activation (hyperthecosis) in the hope of controlling ovarian androgen release. I then stimulate with low dosage FSHr to which I add a smidgeon of LH/hCG (Luveris/Menopur) from the 3rd day and watch for the # of follicles and [E2] starting on the 7th day of COS. If there are > 25 follicles, I keep stimulating (regardless of the [E2] until 50% of all follicles reach 14mm. Then, provided the [E2] is >2500pg/ml, I stop the agonist and the gonadotropin stimulation and follow the E2 (only) daily, without doing further US examinations. The [E2] will almost invariably climb and I watch it go up (regardless of how high the concentration of E2reaches) and track it coming down again. As soon as the [E2] drops below 2500pg/ml (and not before then ever), I administer 10,000U hCGu or hCGf (Ovidrel/Ovitrel-500mcg) as the “trigger” and perform an egg retrieval 36h later. ICSI is a MUST because “coasted” eggs usually have no cumulus oophoris and eggs without a cumulus will not readily fertilize on their own. All fertilized eggs are cultured to blastocyst (up to 6 days). And up to two (2) are transferred transvaginally under US guidance.

The success of this approach depends on precise timing of the initiation and conclusion of “prolonged coasting”. If you start too early, follicle growth will stop and the cycle will be lost. If you start too late, you will encounter too many post-mature/cystic follicles (>22mm) that usually harbor abnormally developed eggs. 

Use of the above approach avoids unnecessary cycle cancellation, severe OHSS, and optimizes egg/embryo quality. The worst you will encounter is mild to moderate OHSS and this too is uncommon.