Stimulation techniques and protocols for poor responders in IVF cycles, future prospective methods and techniques, precaution programs.
Authors: Grigorios A. Hadjopoulos  , Dimas D. Angelos  , Apostolos G. Hadjopoulos  , Harris S. Siristatidis  
Published: March 2023

Purpose: To identify trends regarding approaches, currently used by IVF centers in Greece, in order to treat poor responders. Methods: A retrospective evaluation utilizing the results of a web-based survey was performed. Results: Responses from 36 IVF centers via a web-based survey in Greece was conducted to elucidate optimal treatment strategies of poor responders. IVF specialized Doctors of units with a median of 300 IVF cycles per year were asked to anonymously fill in a set of questions on this complex topic. Results were analyzed, treatment strategies or combinations of protocols or adjuvant therapies used were compared. Also compared number of oocytes retrieved, as well as fertility and pregnancy rates among various IVF centers, based on their responses. A total of 36 centers participated in our survey, (from total 59 IVF centers) forming a web-based questionnaire. Due to responses on question if they observe an increase in the prevalence of poor responders ranging from: 1 - 3 % (8.6%, n=3), 4 - 9% ,(11.1% ,n=4), mainly 20% (47.21% ,n=17), but also greater than 20% (33.3% ,n=12) in total of cases treated in Greek IVF centers. Also, the most common age group of poor responders is 40-50 years of age according to 80%(n=29) of respondents. (Table 1). The review of international medical literature compared with answers received to our questionnaire suggests that no ideal treatment stimulation protocol exist. The following protocols have been described and compared:1).Long protocol with Agonist (25.%,n=9)2).Short protocol with Antagonist (52.8%,n=19)3).Short protocol with Agonist (19.4%,n=7)4).Stimulation only with Gonadotropins (5.6%,n=2)5).Natural Cycle (66.7%,n=24)6).Flare-up protocol (13.9%,n=5)7).Duo-Stim Protocol (11.1%9,n=4)8).Delayed start protocol (11.% ,n=4)9).Protocol with cofifollitropine (13.9%,n=5)10). Clomiphene Citrate Protocol with or without Gonadotropins (41.7%, n=15)11). Clomiphene Citrate Protocol with or without Aromatase inhibitors (19.4%, n=7)12).Letrozole with or without recombinant FSH GnRH Antagonist Use (2.8%, n=1)13). Letrozole with Clomiphene Citrate plus FSH & LH (2.8%, n=1)14). Letrozole with FSH & LH plus GnRH antagonist (2.8%, n=1)15).Protocol with Antagonists in combination with Letrozole(27.8%,n=10) . (Table 2). We also represent results regarding the use of adjuvant treatment modalities to further improve results of stimulation cycles such as: a)Oestrogens(52.2%,n=12),b)Growth Hormone (4.3%,n=1),c)Testosterone (8.7%,n=2),d)Co-enzyme Q10 (56.5%,n=13),e)DHEA (78.3%,n=18). (Table 3). All available therapeutic strategies used and according to international literature and in accordance with data derived from Greek IVF centers, oocyte harvesting ranges at low levels, around 2 to 4 oocytes (88.6% ,n=3), 0-1 (8.6%,n=3), 5-8 (11.4%,n=4) and none of the IVF specialists collected more than 8 oocytes. Oocyte quality is also compromised, in (54.3%, n=19) only one oocyte of A quality was harvested, while 2 and 0, 3 or 4 oocytes of A quality were collected in (49.2%,n=15)and(5.7%,n=2).(Table 4.) , according with data fully verifying the term poor responders. Moreover, we observed that abortion rates are increased >20% (41.2%, n=14), 10-20% (29.4%,n=10), 5-10% (11.8%,n=4) and 1-5% (17.6%,n=6) )(Table 5), as well as pregnancy rates are affected 5-10% (29.4%,n=10) and 10-20% (29.4%,n=10) )(Table 6), while percentages of live pregnancies over 20% is observed in (17,6%,n=6) and under 6% in (23.5%,n=8)(Table 7). Conclusion: All responses from the IVF specialists demonstrate the difficulty of treating this heterogenic group of subfebrile women. The egg donation is the treatment with increased success rate in comparison with different used treatments with agonists , antagonists cc, natural cycle, adjuvant treatments , the success rates of treatment in poor responders in IVF stimulation fluctuates from 7 to 24%. Prognosis is further improved if IVF specialist proposes and proceeds timely to the proper individualized therapeutic strategy.