Μελέτη της φυσιολογίας του φαινομένου δεύτερου ωοθυλακικού κύματος: Αξιολόγηση επιπέδων ελεύθερου κυτταρικού DNA σε ωοθυλακικό υγρό πτωχών απαντητριών, που προκύπτει από την λήψη ωαρίων κατά την ωχρινική φάση, σε φυσικούς κύκλους εξωσωματικής γονιμοποίησης

Η πτωχή ωοθηκική απόκριση αποτελεί μια καλά μελετημένη αιτία υπογονιμότητας, συνοδευόμενη από λίγα ωάρια χαμηλής ποιότητας, γεγονός που οδηγεί σε κακή πρόγνωση των αποτελεσμάτων της εξωσωματικής γονιμοποίησης. Η ετερογένεια της ομάδας αυτής επιφέρει την απουσία ομοφωνίας αναφορικά με τη διάγνωση και τον ορισμό των πτωχών απαντητριών, κάτι που δυσκολεύει τη διαχείρισή τους. Πρόσφατα, η καινοτόμος προσέγγιση της διπλής ωοληψίας κατά τη διάρκεια ωοθυλακικής και ωχρινικής φάσης σε ένα έμμηνο κύκλο έχει εισαχθεί στην κλινική πρακτική της εξωσωματικής γονιμοποίησης. Η ομάδα μας πρότεινε το ακρωνύμιο LuPOR για να περιγράψει την πρακτική της ωοληψίας κατά την ωχρινική φάση. Αυτή βασίζεται σε προηγούμενες παρατηρήσεις σε ζωικά μοντέλα που αναφέρουν την ύπαρξη δύο ή τριών ωοθυλακικών κυμάτων κατά τη διάρκεια ενός έμμηνου κύκλου, το οποίο αντιβαίνει στην υπάρχουσα θεωρία της ωοθυλακιογένεσης. Το προαναφερθέν φαινόμενο είναι γνωστό ως «δεύτερο ωοθυλακικό κύμα» κι έχει εντοπιστεί και στις γυναίκες. Η τρέχουσα βιβλιογραφία εστιάζει στην διπλή διέγερση των ωοθηκών και στη διπλή ωοληψία στον ίδιο εμμηνορρυσιακό κύκλο, δείχνοντας παρόμοιες εμβρυολογικές παραμέτρους από δεδομένα των δυο φάσεων. Επιπλέον, μελέτες που συγκρίνουν την προσέγγιση της διπλής διέγερσης και ωοληψίας με το συμβατικό πρωτόκολλο αποκαλύπτουν ενθαρρυντικά αποτελέσματα αναφορικά με την πρώτη επιλογή, καθώς παρέχει ένα συγκεντρωτικό αριθμό διαθέσιμων ωαρίων σε συντομότερο χρονικό διάστημα. Ωστόσο, ελάχιστα είναι γνωστά σχετικά με την πρακτική της διπλής ωοληψίας κατά τη διάρκεια φυσικών κύκλων εξωσωματικής γονιμοποίησης, αλλά και για την υποκείμενη φυσιολογία του μηχανισμού του φαινομένου του δεύτερου ωοθυλακικού κύματος. Ταυτόχρονα, πολλοί βιοδείκτες έχουν προταθεί για την αξιολόγηση των ωαρίων και εμβρύων, με την καινοτόμο επιλογή του μη επεμβατικού βιοδείκτη του ελεύθερου κυτταρικού DNA (cfDNA) στο ωοθυλακικό υγρό να βρίσκεται στο επίκεντρο της έρευνας. Σκοπός της παρούσας προοπτικής μελέτης είναι να διερευνήσει για πρώτη φορά τη φυσιολογία του φαινομένου του δεύτερου ωοθυλακικού κύματος μέσω της αξιολόγησης των cfDNA επιπέδων στο ωοθυλακικό υγρό από την ωοθυλακική και ωχρινική φάση, σε φυσικούς κύκλους εξωσωματικής γονιμοποίησης. Το προαναφερθέν στοχεύει στο να αποκαλύψει μια πιθανή συσχέτιση του αριθμού και της ωριμότητας των ωαρίων, καθώς και του αριθμού των γονιμοποιημένων ζυγωτών έπειτα από την έγχυση. Ο πληθυσμός της μελέτης αποτελείται από 47 πτωχές απαντήτριες ηλικίας από 32 έως 48 ετών, που έχουν χαρακτηριστεί βάσει των κριτηρίων της Bologna και έχουν ενταχθεί βάσει αυστηρών κριτηρίων ένταξης και αποκλεισμού. Όλες οι γυναίκες ανιχνεύτηκαν με δεύτερο ωοθυλακικό κύμα κι έτσι υποβλήθηκαν σε δεύτερη ωοληψία του ίδιου έμμηνου κύκλου κατά τη διάρκεια φυσικών κύκλων εξωσωματικής γονιμοποίησης. Πραγματοποιήθηκε η προετοιμασία των δειγμάτων ωοθυλακικού υγρού και η επικείμενη απομόνωση του cfDNA, με σκοπό την ποσοτικοποίηση της συγκέντρωσης του cfDNA μέσω της μεθόδου αλυσιδωτής αντίδρασης πολυμεράσης σε πραγματικό χρόνο (RT-PCR). Για την RT-PCR, επιλέξαμε τους εκκινητές ALU115 και ALU247, με τους πρώτους να ενισχύουν τόσο τα μικρά όσο και τα μεγάλα θραύσματα cfDNA, ενώ οι δεύτεροι μόνο τα μεγάλα. Η στατιστική ανάλυση πραγματοποιήθηκε με τη χρήση της R γλώσσας προγραμματισμού. Τα αποτελέσματα έδειξαν ότι η μέση τιμή των επιπέδων των ALU115 ήταν στατιστικά σημαντικά μικρότερη κατά την ωοθυλακική φάση σε σχέση με την ωχρινική (0.79 ± 0.72 vs 1.46 ± 1.59 ng/μl, p-value=0.02). Εστιάζοντας στα αποτελέσματα της ωοθυλακικής φάσης, αποκαλύφθηκε μια στατιστικώς σημαντική συσχέτιση των επιπέδων οιστραδιόλης ορού και συγκέντρωσης ALU115 concentration (p-value=0.04) καθώς και αρνητική συσχέτιση της ακεραιότητας του cfDNA με τα επίπεδα οιστραδιόλης (p-value=0.03). Το τελευταίο παρατηρήθηκε επίσης και στην ομάδα LuPOR (p-value=0.03). Καμία άλλη στατιστικώς σημαντική συσχέτιση δε βρέθηκε μεταξύ των συγκεντρώσεων ALU115, ALU247 και ακεραιότητας cfDNA με οποιαδήποτε παράμετρο που εξετάστηκε. Τέλος, βρέθηκε στατιστικά σημαντικός μικρότερος αριθμός ωαρίων κατά την ωοληψία (1.29±0.58 vs 1.09 ± 0.28, p-value=0.02) και ώριμων ΜΙΙ ωαρίων (0.77 ± 0.55 vs 1.08 ± 0.61, p-value=0.02) αναφορικά με την ωοληψία ωοθυλακικής φάσης, ύστερα από σύγκρισή του με την LuPOR ομάδα. Ωστόσο, καμία στατιστικά σημαντική διαφορά δεν αποδείχθηκε ως προς τον αριθμό των γονιμοποιημένων ζυγωτών. Τα αποτελέσματα αυτά τονίζουν την ποιότητα και της ασφάλεια την ωοληψίας τόσο κατά την ωοθυλακική όσο και κατά την ωχρινική φάση, όπως αξιολογήθηκε μέσω του αποπτωτικού δείκτη του cfDNA. Επιπροσθέτως, ενισχύουν την εγκυρότητα της LuPOR πρακτικής, καθιστώντας την σαν μια εναλλακτική και πολλά υποσχόμενη πρακτική για την χρονοευαίσθητη ομάδα των πτωχών απαντητριών. Ωστόσο, είναι αναγκαία η διεξαγωγή επιπλέον τυχαιοποιημένων μελετών με σκοπό να ενδυναμώσουν τα αποτελέσματά μας σχετικά με την αξιοποίησης της LuPOR πρακτικής σε φυσικούς κύκλους εξωσωματικής γονιμοποίησης.Poor ovarian response represents an in-depth studied etiology of infertility, accompanied with low quantity and quality of oocytes that leads to poor prognosis of in vitro fertilization (IVF) outcomes. The heterogeneity of this group leads to the absence of consensus regarding diagnosis and definition of poor responders, which challenges their efficient management. Recently, the novel approach of double oocyte retrieval during both the follicular and luteal phases of a single menstrual cycle was introduced to IVF clinical practice. Our team introduced the acronym of LuPOR to describe the practice of luteal phase oocyte retrieval. This is based on previous observations in animal models reporting the existence of two or three follicular waves during a single menstrual cycle, which is averse to the prevailing theory of folliculogenesis. The aforementioned phenomenon is known as “Second Follicular Wave”, being also detected in women. Current literature mainly focuses on dual stimulation and dual oocyte retrieval in the same menstrual cycle, indicating similar embryological parameters stemming from data regarding both phases. Moreover, studies that compared the approach of dual stimulation and oocyte retrieval to the conventional protocol, showed encouraging results with respect to the first option, providing a higher cumulative number of available oocytes in a shorter time frame. However, little is known about the practice of double oocyte retrieval during natural cycles, along with the underlying physiology with respect to the mechanism of the second follicular wave phenomenon. Concurrently, numerous biomarkers have been proposed to evaluate oocyte and embryo competency, with the novel option of the non-invasive biomarker of cell-free DNA (cfDNA) in follicular fluid (ff) to be at the spotlight of research. The aim of this prospective study is to uniquely investigate the physiology of the second follicular wave phenomenon, through the evaluation of ff cfDNA levels resulting from follicular and luteal phases of the same menstrual cycle, during natural IVF cycles. The aforementioned intents to reveal a potential association with the number and maturation status of corresponding oocytes, as well as the number of subsequent zygotes following insemination. The study population included 47 poor responders aged from 32 to 48 years, being characterized according to Bologna criteria, and enrolled based on strict inclusion and exclusion criteria. All women were detected with a second follicular wave and thus they underwent double oocyte retrieval in the same menstrual cycle during natural IVF cycles. The preparation of collected ff samples and the subsequent cfDNA extraction were conducted appropriately, resulting in cfDNA quantification through real-time polymerase chain reaction (RT-PCR) method. For RT-PCR, we opted for ALU115 and ALU247 primer sets, with the first to amplify both short and long cfDNA fragments, while the second only the long ones. Statistical analysis was performed employing R statistical programming language. The results showed that the mean levels of ALU115 were statistically significant lower during FoPOR when compared to LuPOR (0.79 ± 0.72 vs 1.46 ± 1.59 ng/μl, p-value=0.02). Regarding FoPOR’s group, a statistically significant positive correlation of serum estradiol levels and ALU115 concentration (p-value=0.04) was revealed, along with a negative correlation of cfDNA integrity and estradiol levels (p-value=0.03). The latter was also observed with respect to LuPOR’s group (p-value=0.03). No other statistically significant difference was observed between ALU115, ALU247 and cfDNA integrity for any of the examined parameters. Finally, a statistically significant lower number of oocyte retrieved (1.29±0.58 vs 1.09 ± 0.28, p-value=0.02) and MII oocytes (0.77 ± 0.55 vs 1.08 ± 0.61, p-value=0.02) regarding FoPOR were recorded when comparing FoPOR to LuPOR groups. However, no statistically significant difference was demonstrated regarding the number of 2PN zygotes. The aforementioned results highlight the quality and safety of performing retrieval in both the follicular and luteal phases, as evaluated through the apoptotic marker of ff cfDNA. Furthermore, they buttress the validity of LuPOR approach, rendering it as an alternative and highly-promising option for the time-sensitive poor responders. However, further randomized controlled trials are imperative to be conducted with the intent to strengthen our results regarding LuPOR practice during natural IVF cycles

Impact of varicocele repair on semen parameters in infertile men: A systematic review and meta-analysis

Purpose: Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly using a before-after analytic approach. No SRMA to date has evaluated the change in conventional semen parameters after VR compared to untreated controls. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls. Materials and Methods: A literature search was performed using Scopus, PubMed, Embase, and Cochrane databases following the Population Intervention Comparison Outcome (PICOS) model (Population: infertile patients with clinical varicocele; Intervention: VR [any technique]; Comparison: infertile patients with clinical varicocele that were untreated; Outcome: sperm concentration, sperm total count, progressive sperm motility, total sperm motility, sperm morphology, and semen volume; Study type: randomized controlled trials and observational studies). Results: A total of 1,632 abstracts were initially assessed for eligibility. Sixteen studies were finally included with a total of 2,420 infertile men with clinical varicocele (1,424 patients treated with VR vs. 996 untreated controls). The analysis showed significantly improved post-operative semen parameters in patients compared to controls with regards to sperm concentration (standardized mean difference [SMD] 1.739; 95% CI 1.129 to 2.349; p<0.001; I2=97.6%), total sperm count (SMD 1.894; 95% CI 0.566 to 3.222; p<0.05; I2=97.8%), progressive sperm motility (SMD 3.301; 95% CI 2.164 to 4.437; p<0.01; I2=98.5%), total sperm motility (SMD 0.887; 95% CI 0.036 to 1.738; p=0.04; I2=97.3%) and normal sperm morphology (SMD 1.673; 95% CI 0.876 to 2.470; p<0.05; I2=98.5%). All the outcomes showed a high inter-study heterogeneity, but the sensitivity analysis showed that no study was sensitive enough to change these results. Publication bias was present only in the analysis of the sperm concentration and progressive motility. No significant difference was found for the semen volume (SMD 0.313; 95% CI -0.242 to 0.868; I2=89.7%). Conclusions: This study provides a high level of evidence in favor of a positive effect of VR to improve conventional semen parameters in infertile men with clinical varicocele. To the best of our knowledge, this is the first SRMA to compare changes in conventional semen parameters after VR with changes in parameters of a control group over the same period. This is in contrast to other SRMAs which have compared semen parameters before and after VR, without reference to a control group. Our findings strengthen the available evidence and have a potential to upgrade professional societies’ practice recommendations favoring VR to improve conventional semen parameters in infertile men

Impact of Varicocele Repair on Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis

Purpose:Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly using a before-after analytic approach. No SRMA to date has evaluated the change in conventional semen parameters after VR compared to untreated controls. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls.Materials and Methods:A literature search was performed using Scopus, PubMed, Embase, and Cochrane databases following the Population Intervention Comparison Outcome (PICOS) model (Population: infertile patients with clinical varicocele; Intervention: VR [any technique]; Comparison: infertile patients with clinical varicocele that were untreated; Outcome: sperm concentration, sperm total count, progressive sperm motility, total sperm motility, sperm morphology, and semen volume; Study type: randomized controlled trials and observational studies).Results:A total of 1,632 abstracts were initially assessed for eligibility. Sixteen studies were finally included with a total of 2,420 infertile men with clinical varicocele (1,424 patients treated with VR vs. 996 untreated controls). The analysis showed significantly improved post-operative semen parameters in patients compared to controls with regards to sperm concentration (standardized mean difference [SMD] 1.739; 95% CI 1.129 to 2.349; pConclusions:This study provides a high level of evidence in favor of a positive effect of VR to improve conventional semen parameters in infertile men with clinical varicocele. To the best of our knowledge, this is the first SRMA to compare changes in conventional semen parameters after VR with changes in parameters of a control group over the same period. This is in contrast to other SRMAs which have compared semen parameters before and after VR, without reference to a control group. Our findings strengthen the available evidence and have a potential to upgrade professional societies' practice recommendations favoring VR to improve conventional semen parameters in infertile men.</p

A Case Series on Natural Conceptions Resulting in Ongoing Pregnancies in Menopausal and Prematurely Menopausal Women Following Platelet-Rich Plasma Treatment

Since the introduction of autologous platelet-rich plasma (PRP) in medical practice, various studies have documented that implementing PRP can enhance healing and the anti-aging process, employing angiogenesis regeneration due to the multiple growth factors and cytokines involved. Numerous reports have shown promising results with the use of PRP in ovarian treatment, regarding ovarian regeneration and reactivation of folliculogenesis. This case series reports on two women with premature ovarian failure (POF) aged 40 and 27 years, respectively, and one menopausal woman aged 46 years. All patients presented with lack of menstrual cycle for over a year. The women reported previous failed in vitro fertilization (IVF) attempts, and, after rejecting the option of oocyte donation, they opted for the approach of autologous ovarian PRP treatment. Following PRP treatment, the three patients were invited to conceive naturally. The primary outcome was the restoration of menstruation following autologous ovarian PRP treatment, as well as an improvement in hormonal profile, a decrease in follicle-stimulating hormone (FSH) levels, and a concurrent increase in anti-Müllerian hormone (AMH) levels. Further to that, our patients achieved pregnancy through natural conception within 2–6 months following PRP treatment, resulting in currently ongoing complication-free clinical pregnancies – a first report in the literature for menopausal and POF patients. Implementation of PRP should be further investigated through randomized controlled trials (RCTs), as it may hold the key to successful treatment for a certain cohort of patients exploring reproductive treatment options following menopause

Empty Zona Pellucida Only Case: A Critical Review of the Literature

The presence of empty zona pellucida (EZP) in oocytes following oocyte retrieval (OR) during an in vitro fertilization (IVF) cycle presents a major clinical and laboratory challenge in assisted reproduction. It has been attributed to several factors such as the ovarian stimulation protocol employed, the damaging of the follicles during oocyte retrieval (OR) mainly through the high aspiration pressure, during the denudation technique, and the degeneration of oolemma within the zona pellucida (ZP) through apoptosis. The role of ZP is pivotal from the early stages of follicular development up to the preimplantation embryo development and embryo hatching. Polymorphisms or alterations on the genes that encode ZP proteins may contribute to EZP. We present a critical review of the published literature hitherto on EZP and available options when encountered with the phenomenon of EZP. Concerning the former, we found that there is rare data on this phenomenon that merits documentation. The latter includes technical, genetic, and pathophysiological perspectives, along with specific treatment options. In conclusion, we identify the lack of a definitive management proposal for couples presenting with this phenomenon, we underline the need for an algorithm, and indicate the questions raised that point towards our goal for a strategy when addressing a previous finding of EZP

Evaluation of the Second Follicular Wave Phenomenon in Natural Cycle Assisted Reproduction: A Key Option for Poor Responders through Luteal Phase Oocyte Retrieval

Background: Emergence of Luteal Phase Oocyte Retrieval (LuPOR) may revolutionize the practice regarding the time-sensitive nature of poor responders ascertaining a higher number of oocytes, in a shorter amount of time. This may be especially important in view of employing the approach of natural cycles for Poor Responders. We suggest the acronym LuPOR describing the clinical practice of luteal phase oocyte retrieval. The aim of the study is to offer insight regarding the identity of LuPOR, and highlight how this practice may improve management of the special subgroup of poor responders. Materials and Methods: The present retrospective observational clinical study includes the collection and statistical analysis of data from 136 poor responders who underwent follicular oocyte retrieval (FoPOR) and subsequent LuPOR in natural cycles, during their In Vitro Fertilization (IVF) treatment, from the time period of 2015 to 2018. All 136 participants were diagnosed with poor ovarian reserve (POR) according to Bologna criteria. The 272 cycles were categorized as follows: 136 natural cycles with only FoPORs (Control Group) and 136 natural cycles including both FoPORs and LuPORs. Results: Our primary results indicate no statistically significant differences with regards to the mean number of oocytes, the maturation status, and fertilization rate between FoPOR and LuPOR in natural cycles. Secondarily, we demonstrate a statistically significant higher yield of oocytes (2.50 &plusmn; 0.78 vs. 1.25 &plusmn; 0.53), better oocyte maturity status (1.93 &plusmn; 0.69 vs. 0.95 &plusmn; 0.59) and higher fertilization rate (1.31 &plusmn; 0.87 vs. 0.61 &plusmn; 0.60) in natural cycles including both FoPOR and LuPOR, when compared to cycles including only FoPOR. Conclusion: Our study may contribute towards the establishment of an efficient poor responders&rsquo; management through the natural cycle approach, paving a novel clinical practice and ascertaining the opportunity to employ oocytes and embryos originating from a luteal phase follicular wave

The Role of Laparoscopic Investigation in Enabling Natural Conception and Avoiding in vitro Fertilization Overuse for Infertile Patients of Unidentified Aetiology and Recurrent Implantation Failure Following in vitro Fertilization

The present study aims to explore the effectiveness of laparoscopic surgery on women presenting with infertility, of unidentified aetiology according to the standard infertility investigation, and recurrent failed In Vitro Fertilization (IVF) attempts. Identifying and correcting possible underlying pathologies by laparoscopy may subsequently enable natural conception in an effort to address infertility and avoid IVF overuse. One-hundred and seven (107) women with unidentified aetiology of infertility and recurrent failed IVF attempts met the inclusion criteria. Laparoscopic surgery was performed as the endpoint of the patients&#8217; diagnostic journey, aiming to identify a possible underlying factor as the cause of infertility. Sixty-two (62) out of 107 patients (57.94%) that underwent laparoscopy were diagnosed with endometriosis, 25 out of the 107 patients (23.3%) were diagnosed with periadnixal and pelvic adhesions, and 20 cases (18.69%) presented with no pathology and remained unexplained. Following identification and correction of endometriosis and pelvic adhesions, patients were invited to conceive naturally. For the patients that laparoscopic investigation failed to reveal any pathology they were categorized as unexplained infertility and were subjected to a single IVF cycle. Natural conception success rate within the first postoperative year was the primary outcome. Within the first postoperative year, 30 out of 62 patients (48.38%) diagnosed with endometriosis following laparoscopic investigation achieved a natural conception, and 28 out of them (93.4%) reported live-births. Additionally, 11 out of 25 patients (44%) diagnosed with periadnixal and pelvic adhesions achieved natural conception within the first operative year. Regarding the group of unexplained infertility patients, only four out of the 20 patients (20%) achieved clinical pregnancy in the first post-operative IVF cycle. In conclusion, laparoscopy appears to be a promising approach, addressing infertility, providing significant diagnostic findings, while avoiding IVF overuse regarding patients of unidentified infertility presenting with recurrent failed IVF attempts

Empty Zona Pellucida Only Case: A Critical Review of the Literature

The presence of empty zona pellucida (EZP) in oocytes following oocyte retrieval (OR) during an in vitro fertilization (IVF) cycle presents a major clinical and laboratory challenge in assisted reproduction. It has been attributed to several factors such as the ovarian stimulation protocol employed, the damaging of the follicles during oocyte retrieval (OR) mainly through the high aspiration pressure, during the denudation technique, and the degeneration of oolemma within the zona pellucida (ZP) through apoptosis. The role of ZP is pivotal from the early stages of follicular development up to the preimplantation embryo development and embryo hatching. Polymorphisms or alterations on the genes that encode ZP proteins may contribute to EZP. We present a critical review of the published literature hitherto on EZP and available options when encountered with the phenomenon of EZP. Concerning the former, we found that there is rare data on this phenomenon that merits documentation. The latter includes technical, genetic, and pathophysiological perspectives, along with specific treatment options. In conclusion, we identify the lack of a definitive management proposal for couples presenting with this phenomenon, we underline the need for an algorithm, and indicate the questions raised that point towards our goal for a strategy when addressing a previous finding of EZP

Introducing intrauterine antibiotic infusion as a novel approach in effectively treating chronic endometritis and restoring reproductive dynamics: a randomized pilot study

The chronic nature of Chronic Endometritis (CE) along with the challenging management and infertility entailed, call for cutting-edge therapeutic approaches. This study introduces the novel treatment of intrauterine antibiotic infusion (IAI) combined with oral antibiotic administration (OAA), and it assesses respective performance against the gold standard treatment of OAA. Data sourced herein reports on treatment efficiency and fertility restoration for both patients aiming to conceive naturally or via In Vitro fertilization. Eighty CE patients, 40 presenting with recurrent implantation failure, and 40 with recurrent pregnancy loss, were enrolled in the IVF and the natural conception arm respectively. Treatment was subjected to randomization. Effectively treated patients proceeded with either a single IVF cycle or were invited to conceive naturally over a 6-month period. Combination of IAI and OAA provided a statistically significant enhanced effectiveness treatment rate (RR 1.40; 95%CI 1.07-1.82; p=0.01). No statistically significant difference was observed regarding the side-effects rate (RR 1.33; 95%CI 0.80-2.22; p=0.52). No statistically significant difference was observed for either arm regarding live-birth rate. Following an intention-to-treat analysis, employment of IAI corresponds to improved clinical pregnancy rate-albeit not reaching statistical significance. In conclusion, complimentary implementation of IAI could provide a statistically significant enhanced clinical treatment outcome

Could the Age Difference of a Single Calendar Year between Patients Undergoing IVF at 34, 35 or at 36 Years Old Affect the IVF Outcome? A Retrospective Data Analysis

Background and Objectives: Clinicians are called to overcome age-related challenges in decision making during In Vitro Fertilization (IVF) treatment. The aim of this study was to investigate the possible impact of a single calendar year difference among patients aged 34, 35 and 36 on IVF outcomes. Materials and Methods: Medical records between 2008 and 2019 were analyzed retrospectively. The study group consisted of women diagnosed with tubal factor infertility. Sample size was divided in three categories at 34, 35 and 36 years of age. Embryo transfer including two blastocysts was performed for every patient. Comparisons were performed regarding hormonal profile, response to stimulation, quality of transferred embryos, positive hCG test and clinical pregnancy rate. Results: A total of 706 women were eligible to participate. Two-hundred and forty-eight women were 34, 226 were 35 while the remaining 232 were 36 years old. Regarding the hormonal profile, the number of accumulated oocytes and the quality of embryos transferred, no statistically significant difference was documented between the three age groups. Women aged 34 and 35 years old indicated a significantly increased positive hCG rate in comparison to women aged 36 years old (p-value = 0.009, p-value = 0.023, respectively). Women aged 34 and 35 years old presented with a higher clinical pregnancy rate in comparison to those aged 36 years old (p-value = 0.04, p-value = 0.05, respectively). Conclusion: A calendar year difference between patients undergoing IVF treatment at 34 or 35 years of age does not appear to exert any influence regarding outcome. When treatment involves patients above the age of 35, then a single calendar year may exert considerable impact on IVF outcome. This observation indicates that age 35 may serve as a valid cut-off point regarding IVF outcome