Validation of the existence of genuine Empty follicle syndrome, versus false empty follicle syndrome to make definitive decisions in cases where recurrent IVF failure encountered secondary to absence of oocytes on ovum pick up-a short communication

Aim: Worldwide a big altercation exists with regards to the actual existence of the term “ Empty follicle syndrome’’(EFS), so much so that certain big authorities in the field have been believing that true EFS does not exist. Basically EFS is a syndrome when no functionally intact oocyte get retrieved when attempting an oocyte pick up (OPU) for a successful in vitro fertilization (IVF), however such patients encounter recurrent IVF failures. Since it is has become a big problem for the treating reproductive endocrinologist, besides the patient encountering recurrent IVF failures, it has become essential to differentiate the true EFS alias genuine Empty follicle syndrome (gEFS) from what is labeled today as the false empty follicle syndrome (fEFS). In view of the recently documented presence of mutations, gEFS got verified and appears to silence this biggest conflict that arose secondary to the existence of a false empty follicle syndrome(fEFS), where one could manage to get successful IVF outcomes subsequent to repeated hCG injections/ gonadotropin releasing hormone (GnRH) agonist in addition to pregnancy, with lot of clinicians believing there is no true term like EFS. Methods: Recently Yang et al., performed a study In tertiary a university based reproductive center in China that was comprised of a big cohort of patients that presented with gEFS. Genetic evaluation was conducted on 35 non correlated infertile patients who went through 16 failed IVF cycles in addition to oocyte degeneration, besides the subjects got a diagnosis of possessing a particular kind of EFS- cumulus oocytes complexes (COC’s) but possessed oocytes that were undergoing degeneration, with the utilization of whole –exome sequencing along with targeted Sanger sequencing. Results: Yang et al., found 22 innovative genetic variant of zona pellucida (ZP), genes in 18 subjects, that were inclusive of 20 variants in ZP 1 gene, 2 in ZP 2 gene in addition to 1 recurring variant in ZP3 gene that had been earlier documented. The homogenous /compound heterogenous ZP 1 mutations were inherited in an autosomal recessive manner, while the heterogenous variants of ZP 2 as well as ZP3 genes possessed an autosomal dominant manner of inheritance. Conclusions: These mutations were anticipated to be harmful in silico along with got further experimentally corroborated to be functionally null dependent on their ectopic expression in vitro. Thus with this further evidence that has been recently provided with regards to the existence of genuine Empty follicle syndrome (gEFS), it is significant for the youngsters to realize if they encounter similar cases after trial of rescue hCG injections / GnRH) agonist, not to further keep waiting, but evaluate further with regards to the existence of mutations for Zona Pellucida (ZP), ZP 1, ZP2 as well as ZP3 genes mutations, or LH/ chorionic gonadotropins receptor (LHCGR) gene mutation without subjecting the patient to repeated IVF, with her psychological as well as financial health in mind

Exploration of the Cytoplasmic Function of Abnormally Fertilized Embryos via Novel Pronuclear-Stage Cytoplasmic Transfer

In regular IVF, a portion of oocytes exhibit abnormal numbers of pronuclei (PN) that is considered as abnormal fertilization, and they are routinely discarded. However, it is known that abnormal ploidy still does not completely abandon embryo development and implantation. To explore the potential of cytoplasm from those abnormally fertilized oocytes, we developed a novel technique for the transfer of large cytoplasm between pronuclear-stage mouse embryos, and assessed its impact. A large volume of cytoplast could be efficiently transferred in the PN stage using a novel two-step method of pronuclear-stage cytoplasmic transfer (PNCT). PNCT revealed the difference in the cytoplasmic function among abnormally fertilized embryos where the cytoplasm of 3PN was developmentally more competent than 1PN, and the supplementing of fresh 3PN cytoplasm restored the impaired developmental potential of postovulatory “aged” oocytes. PNCT-derived embryos harbored significantly higher mitochondrial DNA copies, ATP content, oxygen consumption rate, and total cells. The difference in cytoplasmic function between 3PN and 1PN mouse oocytes probably attributed to the proper activation via sperm and may impact subsequent epigenetic events. These results imply that PNCT may serve as a potential alternative treatment to whole egg donation for patients with age-related recurrent IVF failure.

Management of endometrial polyps in infertile women: A mini-review

Considerable disagreement exists regarding whether endometrial polyps should be removed before attempting natural pregnancy and before pregnancy via intrauterine insemination (IUI) or in vitro fertilization (IVF). Through a literature review, we obtained information on the impact of endometrial polyps and polypectomy on fertility outcomes. Several observational studies have suggested that women with unexplained infertility may benefit from endometrial polypectomy for a future natural pregnancy. A few studies reported benefits from endometrial polypectomy in infertile women who plan to undergo IUI. However, no strong evidence supports polypectomy as a way to improve the pregnancy rate in infertile women who plan to undergo IVF or polypectomy during controlled ovarian stimulation for IVF. Although no studies have defined criteria for the polyp size that should be removed in infertile women, clinicians should be aware that small endometrial polyps (<10 mm) sometimes regress spontaneously. Endometrial polypectomy is currently justified in patients with repeated IVF failure, but more studies are needed to verify that endometrial polypectomy itself will eventually increase the pregnancy rate. Although several mechanisms by which endometrial polyps exert a negative effect on fertility have emerged, there is no consensus about the proper management of endometrial polyps in infertile women. Therefore, the management of endometrial polyps should be individualized depending on the patient's situation and clinician’s preference.

O-215 How common is add-on use and how do patients decide whether to use them? A national survey of IVF patients

Study question How common is IVF add-on use in Australia, and what drives the use? Summary answer Most women (82%) had used one or more IVF add-ons and more than half (54%) first learned about the add-ons from their fertility specialist. What is known already IVF add-ons are procedures, techniques or medicines which may be considered nonessential to IVF, usually used in attempts to improve the probability of conception and live birth. Despite widespread concern about unproven IVF add-ons, information about the prevalence of their use is limited because these data are not available in national registries or datasets. Study design, size, duration Women who had undergone IVF in Australia since 2017 were recruited via social media. Women were excluded if they were gestational surrogates, had used a surrogate, or underwent IVF for oocyte donation or elective oocyte cryopreservation only. Eligible women completed an online survey which was open from 21st June to 14th July 2020. Participants/materials, setting, methods Survey questions included demographics, IVF and medical history, and questions specifically about IVF add-ons such as: the type of add-ons used, information sources consulted, and where participants first heard about add-ons. Women also responded to questions about the importance of scientific evidence regarding safety and effectiveness, factors considered in decision-making around add-on use and the presence of any decision regret. Main results and the role of chance A total of 1,590 responses were analyzed after excluding 287 ineligible responses. Participants were generally representative of women who undergo IVF in Australia in terms of age, indication for IVF, and use of ICSI for fertilisation. Most women had used at least one add-on (82%), and these were usually associated with an additional fee (72%). It was most common to first learn about IVF add-ons from the fertility specialist (54%), and most women reported that they and their specialist contributed equally to the decision to use add-ons. Women viewed scientific evidence for safety and effectiveness as very important on a scale from 0-100, an importance score over 90 was selected by more than half of the participants. Additionally, many (49%) assumed that add-ons were risk-free. Most women experienced regret at the decision to use IVF add-ons (66%), and this regret was greatest among women who experienced IVF failure when using add-ons (83%) and those who believed that the specialist drove the decision to use the add-ons (75%). Limitations, reasons for caution This was a retrospective survey of IVF patients, therefore it may suffer from bias due to patient recall. It does not consider the perspective of the IVF clinic or fertility specialist. Certain questions may be more prone to biased responses, such as those regarding who contributed to decision making. Wider implications of the findings The high prevalence of add-on use is likely generalizable to other settings where IVF treatment is largely private. Although women viewed scientific evidence as very important, most had used unproven IVF add-ons. This might suggest that women were not aware of the lack of robust evidence to support their use. Trial registration number Not applicable

P–392 Clinical outcomes of endometrium receptivity analysis(ERA) testing in patients with repeated IVF failures

Study question Is ERA testing different between RIF patients with control group? Summary answer In RIF patients, there were more chances of non-receptive endometrium. ERA testing may be helpful for the patients with repeated IVF failure. What is known already: The endometrium receptivity analysis testing might have the ability to detect the implantation window. In repeat implantation failure patients, detecting of precisely implantation window may have some benefits. Study design, size, duration This was a single-center retrospective observational study. Two hundred and forty-nine patients who underwent ERA testing following frozen-thawed embryo transfer in our center were including in this study between January 2019 and May 2020. Participants/materials, setting, methods 181 patients having unexplained repeated IVF failure (RIF group, at least tow implantation failure) and 68 patients having no experience with embryo transfer (Control group) who underwent ERA testing were including in this study. Both of Patients having a receptive (R) ERA and having a non-receptive (NR) ERA underwent a personalized embryo transfer (pET) on ERA. ERA results and clinical outcomes compared between RIF group and control group were analyzed by Chi-square test. Main results and the role of chance The proportion of R/NR results were 33:35 for the RIF group and 118:63 for the Control group, demonstrating the displacement of the window of implantation in patients with RIF. Our results revealed an endometrial factor in 51% RIF patients, which was significantly greater than the Control group 34.8% (P = 0.02). Among the patients with NR ERA result, there are not significantly difference in clinical pregnancy rate in the RIF group compared with control group (57.1%. vs. 61.9%). The clinical pregnancy rate of the patients with receptive ERA result also is comparable in both group (70.3% vs. 66.7%). Limitations, reasons for caution This is a retrospective, single center study with limited case number. There were may some bias with ERA testing errors. Wider implications of the findings: In RIF patients, there were more chances of non-receptive endometrium. ERA testing may be helpful for the patients with repeated IVF failure. Larger randomized studies are required to validate these results. Trial registration number 18MMHISO70e

O-025 Value of hysteroscopy

text The 3 main characters in any ART are the uterus, the endometrium, and the embryo. With the rutinary use of 2D US and especially 3D US in infertile patients we are able to assess most of the uterine anomalies and intrauterine pathologies. Until recently, the assessment of the endometrial cavity with hysteroscopy was reserved only for cases of IVF failure, as a complementary evaluation to ensure that nothing was missed during the ultrasound scan. We also need to remember how hysteroscopy was performed in the past and, unfortunately, in some cases even today. In the old days, to assess the endometrial cavity, it was required to take the patient to the operating room and under general anesthesia, dilate the cervix to then introduce a large diameter hysteroscope only for diagnostic purposes. The prevalent working model in ART today is in close collaboration between Fertility specialists, Ultrasound and Hysteroscopy units in order to improve patient’s outcome. In our center, a diagnostic hysteroscopy is performed as part of the diagnostic workup of the infertility patient. It is performed in office setting and without anesthesia, by the staff of the reproduction and infertility unit. When we look at hysteroscopy as an in-office procedure and no longer as a procedure performed in operating room, we appreciate that it is something that all infertility patients can benefit from. The right question to ask now would be “Is there a benefit in performing a hysteroscopy to all our patients?”. Ultrasound is not perfect, especially when evaluating the endometrium. The gold standard and the only modality that we have to assess the endometrium with direct visualization is hysteroscopy. Chronic endometritis, adhesions and adenomyosis are only a few examples of what can be assessed by direct vision of the endometrial cavity. The advantages of a simple, inexpensive, office procedure such as hysteroscopy outweigh any other consideration against it. During my talk all these points will be presented helping to understand why hysteroscopy is becoming an indispensable tool in every assisted fertility unit.

Endometriosis and Adenomyosis Effect on IVF Outcome

Endometriosis is a very common debilitating disease that occurs in 6 to 10 percent of the general female population; in women with pain, infertility, or both, the frequency is 35–50%. Endometriosis is one of the most important causes of infertility. Our objective is to evaluate the effect of endometriosis and adenomyosis on IVF outcome (ongoing pregnancy). 65 women underwent In Vitro Fertilization (IVF) and embryos transfer who had endometriosis with or without adenomyosis were recruited in this retrospective study, resulting in 53.8% had a successful IVF attempt (get pregnant). The highest success rate of IVF was in women who were in mild of endometriosis and IVF failure rate was increased mainly in women who were in severe endometriosis. So, the presence of adenomyosis affects IVF outcome and decreases the rate of implantation.