Experiences and intentions of patients undergoing medically indicated oocyte or embryo cryopreservation: a qualitative study.

STUDY QUESTION: What structural (logistical) and psychological challenges do patients who cryopreserve oocytes or embryos for medical reasons face, including possible barriers to using their frozen materials? SUMMARY ANSWER: The majority of women who underwent oocyte or embryo cryopreservation for medical reasons reported a desire to use their frozen oocytes or embryos but had been impeded by ongoing medical issues, the need for a gestational carrier, or the lack of a partner. WHAT IS KNOWN ALREADY: Current data suggest that many women who have frozen oocytes or embryos for medical indications are concerned about the prospect of infertility and have unique emotional and financial needs that differ from patients with infertility. Further, most patients have not returned to use their cryopreserved materials. STUDY DESIGN, SIZE, DURATION: This is a qualitative interview study of 42 people who cryopreserved between January 2012 and December 2021. Interviews were conducted between March 2021 and March 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: All participants were cisgender women who had undergone oocyte or embryo cryopreservation for medical indications at an academic fertility center. Participants were invited to interview by email if they were younger than 40 years old when their oocytes or embryos were cryopreserved. Interviews were conducted over the internet and transcribed verbatim. Data were analyzed using thematic analysis with the constant comparison method. MAIN RESULTS AND THE ROLE OF CHANCE: Saturation was reached at 42 interviews. The median age of participants was 35 years old (range 28-43) at interview and 31 years old (range 25-39) at cryopreservation. Of the 42 women, 30 had a cancer diagnosis, while 7 had non-cancer chronic medical conditions, and 5 had hereditary cancer susceptibility syndromes. There were 12 women who banked embryos and 30 who banked oocytes. The majority of women indicated a desire to use their cryopreserved materials, but many were unsure about how or when. Four had already used their frozen oocytes or embryos, while another four had conceived without assisted reproduction. The cryopreservation experience was described by the majority as highly emotionally challenging because they felt out of place among couples receiving infertility treatment and, for cancer patients, overwhelmed by the complex decisions to be made in a short time period. Common reported barriers to using frozen materials included ongoing medical issues preventing pregnancy, the need for a gestational carrier, the lack of a partner, and the desire for unassisted conception. Some were glad to have frozen oocytes or embryos to allow more time to meet a partner or if they were considering becoming single parents. LIMITATIONS, REASONS FOR CAUTION: The majority of participants had their oocytes or embryos frozen at a single, urban, academic fertility center, which may limit generalizability. We also could not calculate a response rate because the snowball technique was used to identify additional participants, so did not know the total number of people invited to participate. Like other interview studies, our study may be subject to response bias because those who agreed to participate may have particularly positive or negative views about their experiences. Furthermore, the mean follow-up time since freezing was relatively short (3.3 years, median 2.7 years), which may not have been enough time for some patients to use their frozen materials. WIDER IMPLICATIONS OF THE FINDINGS: Learning about the experiences of patients undergoing medically indicated oocyte and embryo cryopreservation can help clinicians better counsel these patients regarding decisions and hurdles they may encounter. We found that most patients had not returned to use their frozen materials because of ongoing medical issues, the need for a gestational carrier, lack of a partner, or the desire to attempt unassisted reproduction. STUDY FUNDING/COMPETING INTEREST(S): This study did not receive any funding. The authors of this study have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Safety of embryo cryopreservation: insights from mid-term placental transcriptional changes.

BACKGROUND: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms. METHODS: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET). RESULTS: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups. CONCLUSION: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.

Multiple embryo manipulations in PGT-A cycles may result in inferior clinical outcomes.

RESEARCH QUESTION: Do embryos that undergo a thaw, biopsy and re-vitrification (TBR) for pre-implantation genetic testing for aneuploidy (PGT-A) have different ploidy and transfer outcomes compared with fresh biopsied embryos? DESIGN: Retrospective cohort study of all embryos that underwent the following procedures: fresh biopsy for PGT-A (fresh biopsy); embryos that were warmed, biopsied for PGT-A and re-vitrified (single biopsy TBR); embryos with a no signal result after initial biopsy that were subsequently warmed, biopsied and re-vitrified (double biopsy TBR). The patients who underwent transfers of those embryos at a single academic institution between March 2013 and December 2021 were also studied. RESULTS: About 30% of embryos planned for TBR underwent attrition. Euploidy rates were similar after biopsy: fresh biopsy (42.7%); single biopsy TBR (47.5%) (adjusted RR: 0.99, 0.88 to 1.12); and double biopsy TBR 50.3% (adjusted RR: 0.99, 0.80 to 1.21). Ongoing pregnancy over 8 weeks was not statistically significant (double biopsy TBR: 6/19 [31.6%] versus fresh biopsy: 650/1062 [61.2%]) (adjusted RR 0.52, 95% CI 0.26 to 1.03). The miscarriage rate increased (double biopsy TBR: 4/19 [21.1%] versus fresh biopsy: 66/1062 [6.2%])(RR 3.39, 95% CI 1.38 to 8.31). Live birth rate was also lower per transfer for the double biopsy TBR group (double biopsy TBR [18.75%] versus fresh biopsy [53.75%]) (RR 0.35, 95% CI 0.12 to 0.98), though not after adjustment (adjusted RR 0.37, 95% CI 0.13 to 1.09). These differences were not seen when single biopsy TBR embryos were transferred. CONCLUSIONS: Embryos that undergo TBR have an equivalent euploidy rate to fresh biopsied embryos. Despite that, double biopsy TBR embryos may have impaired transfer outcomes.

Fertility preservation in patients undergoing gonadotoxic treatments: a Canadian Fertility and Andrology Society clinical practice guideline.

The management of young patients with cancer presents several unique challenges. In general, these patients are ill prepared for the diagnosis and the impact on their fertility. With the improved survival for all tumour types and stages, the need for adequate fertility counselling and a multidisciplinary approach in the reproductive care of these patients is paramount. Recent advances in cryopreservation techniques allow for the banking of spermatozoa, oocytes, embryos and ovarian tissue without compromising survival. This Canadian Fertility and Andrology Society (CFAS) guideline outlines the current understanding of social and medical issues associated with oncofertility, and the medical and surgical technologies available to optimize future fertility.

ART altered DNA methylation of the imprinted gene H19 in fetal tissue after multifetal pregnancy reduction.

PURPOSE: This study aimed to assess whether assisted reproductive technology alters DNA methylation levels at the H19 promoter and H19 imprinting control element (ICE) in fetal tissues obtained after multifetal pregnancy reduction. METHODS: Fetal tissues from multiple pregnancies were obtained, including fresh and frozen-thawed embryos: nine from conventional in vitro fertilization (c-IVF), four from intracytoplasmic sperm injection (ICSI), ten from cryopreserved IVF embryos (cryo-IVF), and six from cryopreserved ICSI (cryo-ICSI) embryos. Next-generation sequencing-based bisulfite PCR was used to determine the DNA methylation status of three CpG islands (H19-1, H19-2, and H19-3) in the H19 promoter and H19 ICE. The primary outcome was H19-1 DNA methylation status, whereas secondary outcomes assessed H19-2, H19-3, and ICE methylation. RESULTS: The ICSI (ß = -3.189, 95% CI = -5.034 to -1.345, p = 0.0026), cryo-IVF (ß = -2.150, 95% CI = -3.706 to -0.593, p = 0.0129), and cryo-ICSI (ß = -2.238, 95% CI = -3.817 to -0.659, p = 0.0110) groups exhibited significantly lower methylation levels in the primary outcome H19-1 region than the c-IVF group after adjustment. For the secondary outcome H19-2 region, significant decreases were observed in the cryo-IVF (ß = -2.132, 95% CI = -4.071 to -0.192, p = 0.0425) and cryo-ICSI groups (ß = -2.598, 95% CI = -4.566 to -0.630, p = 0.0168). CONCLUSIONS: These findings further indicate that embryo cryopreservation and potentially ICSI can lower the methylation level of the H19 promoter, advocating for careful use of these techniques when necessary.

Counseling and cryopreservation: evaluation of patient-reported counseling and choice on method of cancer-related fertility preservation.

PURPOSE: Prior to cancer treatment, patients make decisions on whether to undergo fertility preservation (FP) and the method of FP. We sought to learn more about counseling and decision-making on the method of cancer-related FP. METHODS: A cross-sectional 26-item online survey was administered to patients with ovaries who underwent cancer-related FP. Associations between demographics and the FP method were made through estimates of risk difference, with a 95% confidence interval. Open-ended responses were analyzed using the constant comparative method. RESULTS: A total of 240 respondents completed the survey: 52% underwent oocyte cryopreservation (OC), 29% underwent embryo cryopreservation (EC), and 19% underwent both oocyte and embryo cryopreservation (OC/EC). Most respondents agreed that if they were to go through the process again, they would make the same decision about FP (80% EC, 72% OC, 59% OC/EC). Women ≥ 35 years reported being counseled more that embryos were superior compared to younger women (risk difference 46%, CI 32.8, 59.1), however were not more likely to freeze embryos (risk difference 6.2%, CI - 9.8, 22.2). Women in long-term relationships reported they were counseled more that embryos were superior compared to those single/dating (risk difference 27%, CI 18.1, 35.9). All women in long-term relationships reported undergoing EC, while the majority of single/dating women reported undergoing OC (74.6%). CONCLUSION: Most women who have undergone cancer-related FP reported they would choose the same FP method again. Women in long-term relationships or ≥ 35 years reported they were more likely to be counseled that EC is superior; however, only women in long-term relationships were more likely to freeze embryos.

Pathways to motherhood: A single-center retrospective study on fertility preservation and reproductive outcomes in patients with breast cancer.

BACKGROUND: Breast cancer treatments often have negative effects on fertility, which pose challenges among patients who want to be parents in the future. This study aimed to examine the efficacy of oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation in patients with breast cancer. METHODS: This retrospective review evaluated 42 patients with breast cancer who underwent fertility preservation at our center from January 2012 to December 2022. This review encompassed the demographic characteristics of the patients, cancer stages, treatment details, and types of fertility preservation procedures and their outcomes. RESULTS: The average age at disease diagnosis was 33.4 years. Approximately 90.4% of patients presented with early-stage cancer (≤2). Of 42 patients, 26 underwent oocyte cryopreservation; 17, embryo cryopreservation; and 2, ovarian tissue cryopreservation. Further, three patients received mixed treatment. The overall live birth rate was 63.2%. There are more live births in embryo cryopreservation group. The successful pregnancy group was significantly younger and had a remarkably higher quantity of preserved oocytes/embryos than the nonsuccessful pregnancy group. The oocyte and embryo utilization rates in cryopreservation were 7.69% and 52.94%, respectively. These findings underscored the importance of prompt, informed discussions about fertility preservation options. CONCLUSION: Fertility preservation in patients with breast cancer have promising reproductive outcomes, with embryo cryopreservation being particularly effective. Prompt counseling and individualized fertility preservation strategies are important for improving the likelihood of posttreatment pregnancy. Nevertheless, future research on the long-term psychological and emotional effects of different fertility preservation methods must be performed.

Reproductive outcomes of embryo cryopreservation and transfer at the start-up phase of fertility preservation in Japan.

Purpose: To verify the effectiveness of embryo transfer (ET) using cryopreserved embryo as fertility preservation (FP). Methods: This study was a questionnaire survey. The total number of embryo cryopreservation (EC) was investigated between 2014 and 2020. And for patients who underwent ET among study period, details of EC, outcome of ET, number of live births, and mortality were investigated. Results: Of the 150 facilities, 114 responded (76.0%). A total of 1420 EC were performed during the study period; and ET was performed for 417 patients. Breast cancer was the most common primary disease. A total of 199 live births (including prospective) were obtained by ET; 1.7 EC and 2.2 ET were performed per patient, and live birth rate was 21.4% per ET (28.1% on 35-37-year-old patients). The number of EC and ET increased with age. The final birth rate, including pregnancies other than FP, was 51.8%. Ovarian stimulation with aromatase inhibitors was commonly used, although with no effect on live birth rates. Random start stimulation was also common, experienced by 36.3% of breast cancer patients. Conclusion: Reproductive outcomes of ETs following EC as FP are acceptable. This research project was registered in the University Hospital Medical Information Network (UMIN000043664).

Live birth rate after female fertility preservation for cancer or haematopoietic stem cell transplantation: a systematic review and meta-analysis of the three main techniques; embryo, oocyte and ovarian tissue cryopreservation.

STUDY QUESTION: What are the chances of achieving a live birth after embryo, oocyte and ovarian tissue cryopreservation (OTC) in female cancer survivors? SUMMARY ANSWER: The live birth rates (LBRs) following embryo and oocyte cryopreservation are 41% and 32%, respectively, while for IVF and spontaneous LBR after tissue cryopreservation and transplantation, these rates are 21% and 33%, respectively. WHAT IS KNOWN ALREADY: Currently, fertility preservation (FP) has become a major public health issue as diagnostic and therapeutic progress has made it possible to achieve an 80% survival rate in children, adolescents and young adults with cancer. In the latest ESHRE guidelines, only oocyte and embryo cryopreservation are considered as established options for FP. OTC is still considered to be an innovative method, while it is an acceptable FP technique in the American Society for Reproductive Medicine guidelines. However, given the lack of studies on long-term outcomes after FP, it is still unclear which technique offers the best chance to achieve a live birth. STUDY DESIGN, SIZE, DURATION: We performed a systematic review and meta-analysis of published controlled studies. Searches were conducted from January 2004 to May 2021 in Medline, Embase and the Cochrane Library using the following search terms: cancer, stem cell transplantation, FP, embryo cryopreservation, oocyte vitrification, OTC and reproductive outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 126 full-text articles were preselected from 1436 references based on the title and abstract and assessed via the Newcastle-Ottawa Quality Assessment Scale. The studies were selected, and their data were extracted by two independent reviewers according to the Cochrane methods. A fixed-effect meta-analysis was performed for outcomes with high heterogeneity. MAIN RESULTS AND THE ROLE OF CHANCE: Data from 34 studies were used for this meta-analysis. Regarding cryopreserved embryos, the LBR after IVF was 41% (95% CI: 34-48, I2: 0%, fixed effect). Concerning vitrified oocytes, the LBR was 32% (95% CI: 26-39, I2: 0%, fixed effect). Finally, the LBR after IVF and the spontaneous LBR after ovarian tissue transplantation were 21% (95% CI: 15-26, I2: 0%, fixed-effect) and 33% (95% CI: 25-42, I2: 46.1%, random-effect), respectively. For all outcomes, in the sensitivity analyses, the maximum variation in the estimated percentage was 1%. LIMITATIONS, REASONS FOR CAUTION: The heterogeneity of the literature prevents us from comparing these three techniques. This meta-analysis provides limited data which may help clinicians when counselling patients. WIDER IMPLICATIONS OF THE FINDINGS: This study highlights the need for long-term follow-up registries to assess return rates, as well as spontaneous pregnancy rates and birth rates after FP. STUDY FUNDING/COMPETING INTEREST(S): This work was sponsored by an unrestricted grant from GEDEON RICHTER France. The authors have no competing interests to declare. REGISTRATION NUMBER: CRD42021264042.

Effect of exposed-to-air frequency of cryopreserved embryo on clinical outcomes of vitrified-warmed embryo transfer cycles: a retrospective analysis of 9,200 vitrified-warmed transfer cycles.

BACKGROUND: Cryopreservation of embryos plays a major role in the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment. However, the storage condition of the cryopreserved embryo can change temporarily due to repeated retrieval of the embryo from the liquid nitrogen (LN2) tank during the practical application during cryopreservation. Whether the implantation potential of a cryopreserved embryo will be damaged when the cane containing it is temporarily exposed to air due to the transfer between the LN2 tank and LN2 container is yet to be elucidated. Also, whether the exposed-to-air frequency (EAF) of cryopreserved embryos influences the clinical outcomes is unclear. OBJECTIVE: To investigate whether the EAF of cryopreserved embryo affects the clinical outcomes of vitrified-warmed embryo transfer. METHODS: A total of 9200 vitrified-warmed embryo transfer cycles were included in this study. All cycles were divided into five groups according to different EAFs (2, 4, 6, 8, or ≥ 10). Post-warming survival rates and clinical outcomes, including implantation, clinical pregnancy and live birth rates were investigated. Kruskal-Wallis test and Pearson's chi-squared tests were used to compare the patient characteristics and clinical outcomes among the five groups. Furthermore, multivariate logistic regression analyses were conducted to investigate the association between EAF and clinical outcomes. RESULTS: No significant differences were observed in the positive HCG rate, implantation rate and live birth rate (P > 0.05) among five EAF groups with respect to D3 embryo, D5 blastocyst and D6 blastocyst. Post-warmed survival rate of D3 embryos (P = 0.015) differed significantly among the five EAF groups, but it was not EAF-dependent. Although clinical pregnancy was different among the five groups with respect to D5 blastocyst (P = 0.042), multivariate logistic regression analysis adjusted for confounding variables suggested that EAF did not adversely affect clinical pregnancy or live birth. CONCLUSION: These findings indicated that human vitrified embryos in the open system could be repeatedly retrieved from the LN2 tank without affecting the implantation potential of the embryo.

Evaluation of live birth rates and perinatal outcomes following two sequential vitrification/warming events at the zygote and blastocyst stages.

PURPOSE: To study the outcome of sequential cryopreservation-thawing of zygotes followed by the cryopreservation-thawing of blastocysts in the course of an IVF treatment on live birth rate and neonatal parameters. METHODS: Single center, retrospective chart review for the time period of 2015-2020. Clinical and perinatal outcomes were compared between frozen embryo transfer cycles utilizing twice-cryopreserved (n = 182) vs. once-cryopreserved (n = 282) embryos. Univariate and multivariable analyses were used to adjust for relevant confounders. RESULTS: After adjustment for maternal age, gravidity, parity, body mass index (BMI), paternal age, fertilization method used, the number of oocytes retrieved in the fresh cycle, fertilization rate, and transfer medium, the transfer of twice-cryopreserved embryos resulted in a reduced probability of live birth (OR, 0.52; 95% CI 0.27-0.97; p=0.041) compared to once-cryopreserved embryos. No differences in the sex ratio, the mean gestational age, the mean length at birth, or the mean birth weight were found between the two groups. CONCLUSION: The circumstantial use of sequential double vitrification-warming in course of treatment is associated with a reduced (but still reasonable) live birth rate compared to once-cryopreserved embryos. As the neonatal outcomes of twice-cryopreserved embryos are similar to once-cryopreserved embryos, this treatment option appears still valid as a rescue scenario in selected cases.

The international transportation of frozen embryos does not affect IVF outcomes.

PURPOSE: The regulated transportation of cryopreserved human embryos resulting from assisted reproduction treatments offers opportunities for patients undergoing embryo transfer in other regions/countries. However, the principal concern for fertility clinics is maintaining unaltered embryo quality to ensure satisfactory clinical outcomes. The aim of the study was to evaluate the efficacy of the transportation process comparing the survival rate and competence of transported embryos to embryos produced and transferred on-site, in frozen embryo transfer cycles. METHODS: This retrospective study assessed the outcomes of 621 blastocysts thawed at IVI Roma (Italy) between March 2021 and March 2022. Autologous or donated oocytes fertilized in vitro, cultured to the blastocyst stage, and cryopreserved in IVI Roma clinic (Group A, n = 450), were compared to embryos generated in IVI Spain clinics and transported to IVI Roma (Group B, n = 171). RESULTS: Groups A and B respectively showed no significant difference in embryo survival rates after thawing (N = 440/450, 97.8% vs. N = 168/171, 98.2%, p = 0.71), pregnancy rates (N = 221/440, 50.23% vs. N = 77/168, 45.83%, p = 0.33), clinical pregnancy rates (N = 200/440, 45.45% vs. N = 62/168, 36.90%, p = 0.06), and miscarriage rates (N = 42/221, 19,00% vs. 21/77, 28.57%, p = 0.13), even after stratification for the source of the oocyte. Logistic binomial regression considering donor oocytes, preimplantation genetic testing, and patients' age, did not show any significant results on embryo survival and IVF outcomes. CONCLUSION: The regulated transport of cryopreserved blastocysts did not affect embryo survival rate or IVF outcomes. Our data support the safety of embryo cryopreservation and medical transportation services, allowing clinics and patients to transport embryos with no significant risk to embryo competence.

Methods and techniques of fertility preservation in patients with endometriosis.

: Objective: Endometriosis is a chronic disease with a relatively high prevalence in the female population. Both the disease itself and its surgical treatment can adversely affect the fertility of patients. For this reason, endometriosis is offered as a possible indication for fertility preservation by cryopreservation methods. The aim of this paper is to present the current knowledge on the options of fertility preservation in this subpopulation. METHODS: Search of relevant literature in PubMed/Medline, Web of Science and Scopus databases. RESULTS: Fertility preservation by cryopreservation methods has so far been used mainly in the care of women with cancer. With increasing experience, the effectiveness and availability of these methods have increased significantly and the indication spectrum has been extended to selected benign diseases such as endometriosis. Three techniques are currently established in practice: embryo cryopreservation, oocyte cryopreservation and ovarian tissue cryopreservation. Oocyte cryopreservation is the most commonly used technique, since it is the most advantageous for the patient and, according to the available data, is an effective way to increase the chances of future pregnancy for patients with endometriosis The purpose is to realize the protection of reproduction before the planned operation. CONCLUSION: The diagnosis of endometriosis negatively affects the fertility of women. For some patients, the solution is fertility preservation by cryopreservation methods. Further clinical studies are needed to define exact, practically applicable indication criteria, potential risks of procedures and their benefits and cost-effectiveness.

Age-specific blastocyst conversion rates in embryo cryopreservation cycles.

RESEARCH QUESTION: What is the blastocyst conversion rate in embryo cryopreservation cycles, per year of female age? DESIGN: Retrospective cohort study including patients undergoing their first ovarian stimulation cycle at our center with planned freeze-all strategy January 1st, 2014-June 30th, 2020. Primary outcome was blastocyst conversion rate. Secondary outcomes included mature oocyte and fertilization rates. Patients were stratified by year of age to assess oocyte yield and embryo development outcomes. RESULTS: 3,362 patients were included. The median blastocyst conversion rate in patients ≤30 was 66.7% (interquartile range 50.0-86.6) and remained statistically comparable through age 40 with a significant decline among ages ≥41 (41-years: marginal effect (ME) -5.2% (-9.7 to -0.7); 42-years: ME -9.6% (-14.3 to -4.8); 43-years: ME -7.7% (-12.8 to -2.6); ≥44-years: ME -20.8% (-26.5 to -15.1)). For the entire cohort, the median mature oocyte rate was 81.8% and the median fertilization rate was 81.8%. The mature oocyte and fertilization rates remained statistically comparable for each year of age except age ≥44 which had a statistically significantly increased mature oocyte rate (ME 4.4% (1.3 to 7.5)) and statistically significantly decreased fertilization rate (ME -5.8% (-9.8 to -1.9)) CONCLUSIONS: In embryo cryopreservation cycles, the blastocyst conversion rate remained statistically comparable through age 40 followed by a statistically significant decline for patients ≥41; however, the mature oocyte and fertilization rates were not impacted by increasing age until age ≥44. Even in women ≥44, over 40% of fertilized oocytes developed to blastocyst. Overall, this information is useful when counseling patients during the embryo culture stage regarding predicted blastocyst yield.

Vanquishing multiple pregnancy in in vitro fertilization in the United States-a 25-year endeavor.

The practice of in vitro fertilization has changed tremendously since the birth of the first in vitro fertilization infant in 1978. With the success of early in vitro fertilization programs in the United States, there was a substantial rise in twin births nationwide. In the mid-1990s, more than 30% of in vitro fertilization cycles resulted in twin or higher-order multifetal pregnancies. Since that time, we not only have witnessed improvements in laboratory and treatment efficacy but also have seen a dramatic impact on pregnancy outcomes, specifically regarding twin pregnancies. Because the field evolved and the risks of multifetal pregnancies became more salient, in 2019, the rate of twin pregnancies had dropped to <7% of cycles. This improvement was largely because of technical advancements and revised professional guidance: culturing embryos longer before transfer, improved freezing technology, embryo preimplantation genetic testing, and revised professional guidance regarding the number of embryos to transfer. These developments have led to single-embryo transfer becoming the standard of care in most scenarios. We used national in vitro fertilization surveillance data of all autologous in vitro fertilization cycles from 1996 to 2019 to illustrate trends in the following improved outcomes: autologous embryo transfer cycles involving blastocyst-stage embryos, vitrified embryos, preimplantation genetic testing cycles, total number of embryos being transferred per cycle, and single-embryo transfer usage over time. Among deliveries from autologous embryo transfers, we highlighted trends in singleton births over time and proportion of deliveries involving twins, triplets, quadruplets, or greater. The notable progress in reducing the rate of multifetal pregnancies with in vitro fertilization was largely attributed to a series of technical and clinical actions, culminating in an 80% reduction in the incidence of multiple births without a loss in overall treatment effectiveness.

Granulocyte-macrophage colony-stimulating factor-containing medium treatment after thawing improves blastocyst-transfer outcomes in the frozen- thawed blastocyst-transfer cycle.

PURPOSE: To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-containing medium could improve embryo-transfer outcomes in frozen-thawed blastocyst transfer. METHODS: Patients who underwent frozen-thawed blastocyst transfer (430 women, aged 30-39 years, 566 cycles) were analyzed. Frozen-thawed blastocysts were cultured in GM-CSF-containing medium or control medium for 3-5 h, followed by transfer to the uterus. The embryo-transfer outcomes in the two groups were measured and compared, and a propensity score matching (1:1) method was used to balance the differences in baseline characteristics. We analyzed 213 matched samples. RESULTS: In patients who underwent frozen-thawed blastocyst transfer with GM-CSF, the percentage of human chorionic gonadotropin-positive cases, biochemical pregnancies, clinical pregnancies, ongoing pregnancies, and live birth rates was 60.6%, 7.98%, 52.6%, 42.9%, and 40.9%, respectively, as compared with 45.1%, 3.29%, 41.8%, 31.1%, and 30.5%, respectively, for the control groups. The rates of human chorionic gonadotropin positivity (odds ratio [OR]: 1.87, 95% confidence interval: [CI]: 1.27-2.75), biochemical pregnancy (2.55, 1.04-6.29), clinical pregnancy (1.54, 1.05-2.27), ongoing pregnancy (1.64, 1.13-2.41), and live birth (1.67, 1.14-2.45) were significantly higher in the GM-CSF group than the control group. The incidence of pregnancy loss (22.3% vs. 27.0%) did not significantly differ between the groups. CONCLUSION: The use of a GM-CSF-containing medium for blastocyst-recovery culture improved the live birth rate as a result of increased implantation rate in the frozen-thawed blastocyst-transfer cycle. The use of GM-CSF-containing medium following blastocyst thawing could be an effective choice for improving the blastocyst-transfer outcomes.

Hereditary breast cancer and fertility preservation outcomes.

PURPOSE: To determine the frequency of hereditary breast cancer associated with different mutated genes and to evaluate fertility preservation (FP) outcomes among young women with hereditary breast cancer when compared to non-hereditary breast cancer. MATERIAL AND METHODS: A retrospective cohort study of women with breast cancer who underwent fertility preservation treatment at our academic fertility center between 2005 and 2019. We included all women with breast cancer aged < 40 years who had a genetic testing and underwent fertility preservation before starting gonadotoxic therapy (n = 132). Our objective was to evaluate the total number of oocytes retrieved, mature oocytes MII, embryos (where appropriate), cryopreserved oocytes, and/or embryos. RESULTS: Of 132 women with breast cancer, 40 women were found to be genetically positive (31.4%), 31 women of 40 (77.5%) had a BRCA mutation, 3 (7.5%) had ATM, 2 (5%) had CHK2, and one (2.5%) for each of the following genes: PALP2, NF, MUTYH.c.536A, and TP53. There was no significant difference between the groups in the total number of eggs retrieved and the number of MII oocytes and cryopreserved oocytes. The numbers of fertilized oocytes and cryopreserved embryos in the hereditary (n = 40) and non-hereditary (n = 92) group were (5.15 ± 6.6 vs 2.90 ± 4.2, P = 0.054) and (3.35 ± 3.7 vs 1.9 ± 2.8, P = 0.046) respectively. CONCLUSION: More than three quarters of positive mutated genes in women with breast cancer are BRCA mutations. Compared to those with non-hereditary breast cancer, women with hereditary breast cancer attained higher number of cryopreserved embryos.

Are commercial warming kits interchangeable for vitrified human blastocysts? Further evidence for the adoption of a Universal Warming protocol.

PURPOSE: To study whether a new combination of different warming kits is clinically effective for vitrified human blastocysts. METHODS: This is a longitudinal cohort study analysing two hundred fifty-five blastocysts warming cycles performed between January and October 2018. Embryos were vitrified using only one brand of ready-to-use kits (Kitazato), whereas the warming procedure was performed with three of the most widely used vitrification/warming kits (Kitazato, Sage and Irvine) after patient stratification for oocyte source. The primary endpoint was survival rate, while the secondary endpoints were clinical pregnancy, live birth and miscarriage rates. RESULTS: We observed a comparable survival rate across all groups of 100% (47/47) in KK, 97.6% (49/50) in KS, 97.6% (41/42) in KI, 100% (38/38) in dKK, 100% (35/35) in dKS and 100% (43/43) in dKI. Clinical pregnancy rates were also comparable: 38.3% (18/47) in KK, 49% (24/49) in KS, 56.1% (23/ 41) in KI, 47.4% (18/38) in dKK, 31.4% (11/35) in dKS and 48.8% (21/ 43) in dKI. Finally, live birth rates were 29.8% (14/47) in KK, 36.7% (18/49) in KS, 46.3% (19/41) in KI, 36.8% (14/38) in dKK, 25.7% (9/35) in dKS and 41.9% (18/43) in dKI, showing no significant differences. CONCLUSION: This study confirmed the efficacy of applying a single warming protocol, despite what the "industry" has led us to believe, supporting the idea that it is time to proceed in the cryopreservation field and encouraging embryologists worldwide to come out and reveal that such a procedure is possible and safe.

Controlled ovarian stimulation outcomes of fertility preservation procedures in newly diagnosed breast cancer patients: a retrospective study from a single-tertiary-IVF centre.

The aim of this study was to evaluate the effectiveness of controlled ovarian stimulation (COS) using the letrozole-supplemented stimulation protocol in breast cancer (BC) patients prior to their cancer treatment. Sixty-one BC patients (Stages 0-3) who were referred to a university IVF unit for fertility preservation (FP) and underwent embryo and/or oocyte cryopreservation between 2008 - 2020 were included in this retrospective study. Time intervals between breast surgery and initial fertility consultation (IFC)/completion of FP procedures were evaluated. COS outcomes were assessed and compared between the early follicular phase (EFP) and the random-start (RS) protocols. The patients' mean age was 33.3 ± 4.9 years. The mean time interval between breast surgery and IFC was 20.6 ± 11 (day, mean ± SD) and from IFC to completion of FP procedure was 14.7 ± 5.3. Overall, 9.1 ± 5.9 mature oocytes were obtained, with a peak serum oestradiol level of 388 ± 358 pg/mL. The number of oocytes obtained (11.5 ± 9.3 vs. 10.9 ± 6.9, p = .9) and maturation rates (84.3 ± 17.5% vs. 89.2 ± 11.7, p = .5) were not statistically different between the EPF and RS protocols. The study results support that oocyte or embryo freezing can be performed effectively in a limited time period with letrozole-supplemented COS protocols before the initiation of oncological treatments in breast cancer patients.Impact statementWhat is already known on this subject? Currently, embryo and oocyte freezing are considered the most established fertility preservation (FP) methods for newly diagnosed cancer patients.What do the results of this study add? This study reports the COS outcomes of newly diagnosed breast cancer patients for FP over a period of twelve years from a single IVF unit. The results support that a considerable number of oocytes can be harvested with letrozole-supplemented COS protocol, which appears to be an effective protocol for BC patients.What are the implications of these findings for clinical practice and/or further research? There is a need for additional studies evaluating long-term follow-up of patients with their pregnancy outcomes.

Female fertility preservation in cancer patients.

Fertility preservation in cancer patients or oncofertility is a relatively new trend in modern medicine. In patients with unfulfilled reproductive plans, the possibility of starting a family is one of the key parameters of quality of life after overcoming a cancer. Guidelines have existed since 2013 and in 2020 the European Society of Human Reproduction and Embryology has also published a guideline, but the main problem of their application in clinical practice is the lack of information for both patients and, unfortunately, professionals, as well as the high cost of treatment. From 2022, health insurance companies in the Czech Republic partially cover the expenses for fertility preservation treatment for cancer patients. The possibilities of oncofertility are based, on the one hand, on improving the results of oncological treatment, on the other hand, on the development of reproductive technologies. Thanks to progress in treatment, up to 80% of pediatric oncology patients survive into adulthood, but chemotherapy, especially highly effective alkylating agents, is associated with a high risk of impaired fertility. This article overviewed9 modern global trends of fertility preservation in women undergoing cancer treatment based on an analysis of the English-language literature over the past 5 years.