Dissertation committee:
Κουτσιλιέρης Μιχαήλ, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μαυραγάνη Κλειώ, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ασημακόπουλος Βύρωνας, Καθηγητής, Ιατρική Σχολή, ΔΠΘ
Νικολέττος Νικόλαος, Καθηγητής, Ιατρική Σχολή, ΔΠΘ
Σιμοπούλου Μαρία, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Φιλίππου Αναστάσιος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Καλαμπόκας Θεόδωρος, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Animal models, particularly domestic animals such as horses and cattle were the first species that the second follicular wave in the same menstrual cycle was investigated. The second fol-licular wave has been presented as a mean to enhance the context of in vitro fertilization (IVF) success rates for infertile women and especially for POR patients. Double ovarian stimu-lation combined to two oocyte retrievals in the same menstrual cycle has been suggested as a promising approach to improve reproductive outcome. However, the population variation characterizing POR patients suggests that studies should investigate factors indicating effi-cient LuPOR application. This study aims to develop a prediction model indicating successful implementation of Luteal Phase Oocyte Retrieval (LuPOR) in poor responders, as defined by the retrieval of at least one MII oocyte.
For this retrospective observational study, conducted between 2012–2020, recruited 1688 women diagnosed with POR, undergoing natural IVF cycles with double oocyte retrieval in the same menstrual cycle. Maternal age, BMI, number of previous POR incidences, basal hormonal levels, AFC, E2 evaluated on both follicular and luteal phase trigger day and number of small follicles (8–13 mm) were assessed as predictive factors of the success of LuPOR im-plementation. The inclusion criterion for this study was the diagnosis of POR according to Bo-logna criteria, while women with any other infertility etiologies were ruled out. Stratification of patient dataset was performed in quantiles according to age. A random 20% of each quan-tile was employed in the validation of the model, while the remaining 80% was employed in the development of this model. The predictive value was evaluated employing the Area Un-der the Curve (AUC) of the Receiver Operating Characteristics, employing Youden’s index.
Maternal age, BMI, number of previous failed IVF cycles, basal levels FSH, LH, prolactin and progesterone do not seem to provide predictive value of a successful LuPOR (AUC=0.6). AFC with a threshold value of 4.47, may constitute a predictive factor of an effective LuPOR with an AUC of 0.86, sensitivity 0.8, specificity 0.75, and accuracy 0.79. E2 levels evaluated on the FoPOR trigger day as well as on the LuPOR trigger day, presented with threshold values of 232.66 pg/ml and 200.89 pg/ml, respectively. FoPOR E2 was found to be predictive of the presence of at least one MII oocyte during LuPOR, presenting with an AUC 0.86, specificity 0.75, sensitivity 0.86 and accuracy 0.82. Similarly, LuPOR E2 was found with an AUC 0.89, speci-ficity 0.85, sensitivity 0.95 and accuracy 0.92. The number of small follicles during FoPOR was found to be predictive of of an effective LuPOR, with a threshold value of 2.94. The AUC was 0.82, specificity 0.75, sensitivity 0.76 and accuracy 0.75. Combining the above parameters led to the development of a predictive model with AUC 0.88, specificity 0.73, sensitivity 0.94 and accuracy 0.89. The positive and negative predictive value of the model were 93.5% and 46.8%, respectively.
This study includes solely natural cycles IVF which may be a limitation, as the threshold values presented herein may be altered in COS cycles. Considering that this was a single center study employing internal validation, which may add a further confounder, external validation is required.
This study suggests that parameters like AFC, number of small follicles, and E2 levels on Fo-POR and LuPOR trigger days, may predict successful LuPOR application, defined as the pres-ence of at least one MII oocyte during LuPOR. Reporting back to the practitioner, this study provides a predictive model identifying the optimal POR population for whom LuPOR practice is valuable. The high positive predictive value of this model may facilitate the identification of patients who will benefit from double stimulation protocol.
Keywords:
Assisted reproduction, In vitro fertilization, Second follicular wave, Luteal phase, Oocyte retrieval
