Placental Dysfunction in Assisted Reproductive Pregnancies: Perinatal, Neonatal and Adult Life Outcomes

Obstetric and newborn outcomes of assisted reproductive technology (ART) pregnancies are associated with significative prevalence of maternal and neonatal adverse health conditions, such as cardiovascular and metabolic diseases. These data are interpreted as anomalies in placentation involving a dysregulation of several molecular factors and pathways. It is not clear which extent of the observed placental alterations are the result of ART and which originate from infertility itself. These two aspects probably act synergically for the final obstetric risk. Data show that mechanisms of inappropriate trophoblast invasion and consequent altered vascular remodeling sustain several clinical conditions, leading to obstetric and perinatal risks often found in ART pregnancies, such as preeclampsia, fetal growth restriction and placenta previa or accreta. The roles of factors such as VEGF, GATA3, PIGF, sFLT-1, sEndoglin, EGFL7, melatonin and of ART conditions, such as short or long embryo cultures, trophectoderm biopsy, embryo cryopreservation, and supraphysiologic endometrium preparation, are discussed. Inflammatory local conditions and epigenetic influence on embryos of ART procedures are important research topics since they may have important consequences on obstetric risk. Prevention and treatment of these conditions represent new frontiers for clinicians and biologists involved in ART, and synergic actions with researchers at molecular levels are advocated.

Effectiveness of Cryopreservation in Patients of Young Reproductive Age with the Risk of Ovarian Hyperstimulation, "Thin" Endometrium and Previous IVF Failures

The article provides an analysis of clinical, anamnestic and laboratory parameters for patients of young reproductive age who participated in IVF programs and have cryopreserved embryos. The main reasons for embryo cryopreservation were prevention of OHSS, "thin" endometrium and "previous IVF failures." It has been found that the patients from the group of transfer cancellation due to prevention of ovarian hyperstimulation had a higher ovarian reserve, a larger number of eggs, fresh and frozen embryos, and shorter shelf life of frozen embryos. All embryos were of the best quality (corresponding to the day of cultivation); the “post-thaw cultivation” technique was applied. During stimulation, lower amounts of gonadotropins were used. Patients with thin endometrium and previous IVF failures demonstrated slow growth of follicles, which required a higher course dose of gonadotropins with the addition of LH-containing preparations. Regardless of the group, in most cases, frozen/thawed embryos were transferred at the blastocyst stage (Day 5). The pregnancy rate was high in patients at risk of OHSS and with thin endometrium (48.6%, 48.0%). Patients with IVF failures had a lower pregnancy rate; this is due to endometrial pathology in the medical history, a smaller number of antral follicles, oocytes, fresh and frozen embryos, and longer shelf life of frozen embryos.

Infrastructure of Fertility Preservation Services for Pediatric Cancer Patients: A Report From the Children's Oncology Group

PURPOSE Fertility preservation (FP) services are part of comprehensive care for those newly diagnosed with cancer. The capacity to offer these services to children and adolescents with cancer is unknown. METHODS A cross-sectional survey was sent to 220 Children's Oncology Group member institutions regarding institutional characteristics, structure and organization of FP services, and barriers to FP. Standard descriptive statistics were computed for all variables. The association between site-specific factors and selected outcomes was examined using multivariable logistic regression. RESULTS One hundred forty-four programs (65.5%) returned surveys. Fifty-three (36.8%) reported a designated FP individual or team. Sperm banking was offered at 135 (97.8%) institutions, and testicular tissue cryopreservation at 37 (27.0%). Oocyte and embryo cryopreservation were offered at 91 (67.9%) and 62 (46.6%) institutions, respectively; ovarian tissue cryopreservation was offered at 64 (47.8%) institutions. The presence of dedicated FP personnel was independently associated with the ability to offer oocyte or embryo cryopreservation (odds ratio [OR], 4.7; 95% CI, 1.7 to 13.5), ovarian tissue cryopreservation (OR, 2.7; 95% CI, 1.2 to 6.0), and testicular tissue cryopreservation (OR, 3.3; 95% CI, 1.4 to 97.8). Only 26 (18.1%) participating institutions offered all current nonexperimental FP interventions. Barriers included cost (70.9%), inadequate knowledge or training (60.7%), difficulty characterizing fertility risk (50.4%), inadequate staffing (45.5%), and logistics with reproductive specialties (38%-39%). CONCLUSION This study provides the most comprehensive view of the current landscape of FP infrastructure for children and adolescents with cancer and demonstrates that existing infrastructure is inadequate to offer comprehensive services to patients. We discuss modifiable factors to improve patient access to FP.

Alterations of miR-16, miR-let-7a and their target genes expression in human blastocysts following vitrification and re-vitrification

Embryo cryopreservation is a widely used technique in infertility management and today is an essential part of assisted reproductive technology (ART). In some cases, re-vitrification can be applied to good quality supernumerary warmed embryos that have not been transferred in the present cycle. However, there is no study about re-vitrification impact on microRNA and gene expression in human embryos. The purpose of this study is to evaluate miR-16, miR-let7a and target genes expression in in vitro produced human blastocysts following re-vitrification.Day3 embryos obtained from ICSI cycles of fertile couples referring for family balancing program were biopsied and cultured individually. On the fourth day (post-ICSI) male ones (choices of their parents) were transferred and the females (good quality embryos) were donated for research. Donated embryos were cultured to blastocyst stage and assigned to three groups: fresh, vitrified and re-vitrification. Embryos were vitrified on Cryotech carriers. Then blastocysts of three groups were individually assessed for expression of miR-16, miR-let7a and target genes.The results showed that re-vitrification of human blastocysts did not affect the ability to re-expand in culture. In addition, significant decrease was observed in miR-16 and miR-let7a expression in re-vitrified group compared to fresh (p < 0.05). A significant upregulation of the target genes ITGβ3 and BCL-2 in re-vitrified and vitrified embryos was observed compared to the fresh group (p < 0.05). The expression of BAX as a pro-apoptotic gene showed a significant decrease in re-vitrification group comparing with the fresh one (P < 0.05).The results of this research indicated that re-vitrification of embryos changes the expression of miR-16, miR-let-7a and their target genes. These alterations include increased expression of BCl-2 and ITGβ3 genes which play important roles in embryo survival and implantation, respectively. Clinical proof of these effects requires further research.

Fertility Preservation Programme in a Tertiary-Assisted Reproduction Unit in Hong Kong

Background: Fertility preservation is increasingly important with improving cancer survival rates and the delay in childbearing in modern societies. The objective of our study was to review the experience of the fertility preservation programme in a tertiary-assisted reproduction unit in Hong Kong. Methods: This is a retrospective study involving men and women who were seen at a tertiary-assisted reproduction unit for fertility preservation counselling before gonadotoxic treatment from January 2005 to December 2020. Their medical records in paper and electronic forms were reviewed. Results: There were 75 consultations for female fertility preservation from 2010 to 2020 involving 72 women. Twenty women underwent 22 cycles of ovarian stimulation for oocyte or embryo cryopreservation, two of whom subsequently transported their oocytes abroad for further management and another two achieved natural conception. Additional four women who did not have oocyte or embryo cryopreservation achieved natural conception after cancer treatment. Eleven (15.2%) women were followed up at a reproductive endocrinology clinic after their cancer treatment. From 2005 to 2020, 265 men had sperm cryopreserved. Twenty-six (9.8%) came back to use the cryopreserved sperms, the wives of 13 (50.0%) of whom achieved an on-going pregnancy. Six of them transferred out and 40 discarded the cryopreserved sperms. Conclusions: There was generally an increasing number of patient consultations for fertility preservation in our Centre over the past decade but a consistently low rate of utilisation of cryopreserved gametes for both women and men. Post-cancer treatment fertility evaluation and monitoring was a major area of deficiency in Hong Kong. More structured post-cancer treatment fertility follow-up is needed.

A retrospective study evaluating the impact of scattering radiation from imaging procedures on oocyte quality during ovarian stimulation for fertility preservation in young breast cancer patients

Purpose Ovarian stimulation for oocyte and embryo cryopreservation is the standard of care for fertility preservation in young breast cancer patients before gonadotoxic chemotherapy. The procedure should be started as soon as possible to avoid delay of treatment; thus, it is often performed concomitantly with tumor staging assessments. However, questions remain regarding the potential negative impact on oocyte quality that may occur due to exposure to scattered ionizing radiation from imaging techniques when staging assessment is conducted at the same time as ovarian stimulation. Methods We conducted a retrospective study on all breast cancer patients who received ovarian stimulation for fertility preservation at our center between November, 2012 and May, 2020. Results Gynecologic and oncologic characteristics were similar between patients exposed (n = 14) or not (n = 60) to ionizing radiation. Exposed patients started the ovarian stimulation sooner after diagnosis than non-exposed patients (11.5 vs 28 days, respectively, P < 0.01). Cycle parameters, including the median number of oocytes collected (10.5 vs 7, P = 0.16), maturation rates (92.5% vs 85.7%, P = 0.54), and fertilization rates (62.2% vs 65.4%, P = 0.70) were similar between groups. Conclusions This study shows that scattered ionizing radiation due to staging assessment appears to be safe without compromising follicular growth and maturation. Larger studies on fertility and obstetrical outcomes are needed to confirm these preliminary data.

Adult cancer patients and parents of younger cancer patients have little information about fertility preservation: a survey of knowledge and attitude

Background Impaired fertility is one of the side effects of effective cancer therapy. Saving the potential or storing the material to enable people to have biological children after cancer treatment can be of high importance to many cancer survivors. Therefore, we designed a study to determine knowledge and attitudes to fertility preservation (FP) in adult cancer patients and the parents of patients with cancer. Participants who completed this survey were a convenience sample of 384 parents of cancer patients < 18 years and cancer patients ≥ 18 years from two large referral hospitals. A 25-item self-administered questionnaire measured knowledge and attitudes to FP. Responses were yes/no, or on a 4-point Likert scale (greatly, usually, rarely, never) scored from 1 for never to 4 for greatly. Results Most parents and most cancer patients were unaware of the FP methods of embryo cryopreservation (96.3% and 88.4%, respectively) and sperm cryopreservation (97.5% and 89.0%, respectively). Attitudes among cancer patients and parents to use of FP options, based on a 4-point Likert scale, were determined by financial cost, lack of access and information on FP options. Conclusion Of concern in this sample of Iranian adult cancer patients and their parents is that knowledge of the fertility risk associated with cancer therapy and knowledge of FP treatment options was generally poor, particularly among the parents. To enable cancer patients or their parents to make the best decisions about using FP services, oncologists and fertility specialists should discuss FP options during their consultation.

P–457 Emergency fertility preservation (FP) in female patients- utilisation rate of the stored eggs/embryos and pregnancy outcomes

Study question The aim of the study was to determine the percentage of patients returning to use their stored eggs/embryos following FP and their pregnancy outcomes. Summary answer The patient utilisation rate for eggs/embryos was 17% with a live birth rate of 59%. What is known already Fertility preservation is considered as a vital issue for individuals in the reproductive stage of life when their future fertility may be compromised. Increased cancer survival rate and advances in assisted reproductive techniques make this an essential service to offer to patients facing life limiting disease or long-term medical conditions.FP is important to improve the quality of life in cancer survivors. Study design, size, duration A retrospective analysis was performed over a period of ten years between January 2010 to December 2020 in our tertiary unit. A total of 75 patients who underwent FP were identified. Participants/materials, setting, methods Infertility database for embryology and andrology (IDEAS) was used for the data collection and analysis. Patient’s age, reasons for fertility preservation, type of benign/cancer condition, protocol used for controlled ovarian stimulation (COS), dose of the gonadotropins, number of eggs collected, number of eggs/embryos cryopreserved, duration between storage and fertility treatment, pregnancy outcomes were included in the analysis. Main results and the role of chance Seventy-five patients underwent FP during the 10-year study period. The mean age was 30 years (range 17–43). Seventy-two patients (96%) underwent treatment for oncological reasons and the rest (4%) were for gender transition and Crohn’s disease. The most common types of malignancies include breast cancer (36%), Hodgkin’s lymphoma (18%) and cervical cancer (15%). Ninety-two percentage of patients underwent COS with an antagonist cycle, with an average of 10.8 eggs collected. Recombinant follicle stimulating hormone (FSH) was used in 92% of the cycles and human menopausal gonadotropin (HMG) was used in 8%. Fifty-eight percentage were given a maximum dose of 300IU of gonadotropin. The mean yield of eggs was higher in patients with breast cancer (12.62) followed by Hodgkin’s (10.5) and cervical cancer (9.6). Majority (60%) had embryo cryopreservation (82% at blastocyst stage and 18% at day 3 cleavage stage) and the rest (40%) had egg cryopreservation. A total of 17% (12) of patients returned for treatment with a livebirth rate of 59% and miscarriage rate of 8%. One third of livebirths were achieved through surrogacy. The average duration between fertility preservation and return for treatment was 2.4 years. Limitations, reasons for caution During the last 5 years, there has been an increase in the number of young women requiring FP in our unit. These women may require a considerable amount of time to complete their oncological treatment before embarking on pregnancy using their stored eggs/embryos. Wider implications of the findings: As cancer survival rate improves, there will be a likely increase in the utilisation rate for follow up treatment among young women who had FP. The overall awareness of the gonadotoxic effect of cancer therapy and available fertility preservation options among both patients and clinicians needs to be increased. Trial registration number NA