Unsuccessful IVF Cycles Research Articles

Robotic-assisted excision of diffuse adenomyosis.

Adenomyosis is a chronic, debilitating condition characterised by the presence of endometrial- like glands and stroma within the myometrium. While hysterectomy remains the definitive treatment, uterus- sparing surgeries may be a possible option for patients desiring to maintain fertility. Surgical management, along with medical treatment and/or Assisted Reproductive Technology (ART), can improve outcomes. To provide a step-by-step video demonstration of robotic-assisted excision of diffuse adenomyosis affecting the posterior uterine wall. This video article describes the use of a robotic platform in conjunction with intracavitary indocyanine green (ICG) for the uterus-sparing excision of diffuse adenomyosis. Perioperative data, specifics of the surgical approach, and both objective and subjective outcomes of this surgical approach. A 38-year-old nulligravid patient with a history of chronic pelvic pain and infertility underwent surgical management of adenomyosis following two unsuccessful IVF cycles. The excisional surgery resulted in minimal blood loss (60 ml) and the patient was discharged on the same day of surgery with no complications. In select patients, robotic-assisted surgical management of diffuse adenomyosis can be advantageous. Leveraging the benefits of robotic technology, combined with appropriate surgical techniques, facilitates the performance of extensive surgeries with minimal morbidity and favourable outcomes.

P-730 Detection of mitochondrial reversal following meiotic spindle transfer: a finding of importance for mitochondrial replacement therapies used for the purpose of avoiding mtDNA disease transmission

Abstract Study question Following transfer of the meiotic spindle from a patient’s oocyte into an enucleated donor oocyte, do relative levels of patient and donor mtDNA remain stable? Summary answer mtDNA transferred along with the patient’s spindle typically remain at a low level. However, disproportionate expansion of the patient’s mtDNA can occur in some cases. What is known already Mitochondrial DNA disorders are caused by mutations in the mitochondrial genome, disrupting ATP production. They have few treatment options and no cure. All mitochondria are derived from the oocyte, therefore mtDNA disorders are maternally inherited. It has been proposed that disease transmission could be avoided if female mtDNA mutation carriers underwent meiotic spindle transfer (MST), removing the chromosomes (on the spindle) from an affected oocyte and transferring them into the healthy cytoplasm of a donor oocyte. However, research using embryonic stem cells has suggested that the small population of mitochondria transferred along with the spindle can sometimes undergo dramatic expansion. Study design, size, duration 25 infertile couples were enrolled in a prospective pilot study evaluating MST as a treatment for infertility. The female participants had a mean age of 37.2, and an average of 6.4 previous unsuccessful IVF cycles (range 3-11) characterised by extremely poor embryo development and without any previous pregnancy. Importantly, none of the patients were carriers of a mtDNA disorder. Oocyte donors with previous successful IVF outcomes were matched with patients according to standard practice. Participants/materials, setting, methods Metaphase-II-spindles from patient oocytes were transferred into enucleated donor oocytes. Reconstructed oocytes underwent ICSI and the resulting embryos were transferred at the blastocyst stage. Mitochondrial genomes were sequenced to identify polymorphisms differing between the patient and oocyte donor. These variations were quantified in the embryos (blastocyst biopsies), during pregnancy (amniocentesis), in newborns (cord blood, cord tissue, urine), at 3-6 months and at one year (saliva, urine, blood), revealing the relative amounts of each mitochondrial type. Main results and the role of chance This MST pilot study resulted in the birth of six children, indicating that the procedure is compatible with the production of viable embryos, capable of producing healthy live births. The patient’s mtDNA was shown to represent <1% of the total in all blastocysts produced, confirming that MST is highly reproducible and that relatively few mitochondria are transferred along with the spindle. For five of the six children, the proportion of the total mtDNA attributable to the patient appeared to be stable, remaining at very low levels in all of the samples from later developmental stages. However, in one child the small quantity of mtDNA transferred along with the spindle increased disproportionately with respect to the mtDNA of the oocyte donor, ultimately representing 30-60% of the total at birth, depending on the tissue tested. The precise timing of the expansion of one type of mtDNA at the expense of the other is not known but occurred sometime between the blastocyst stage and birth. By the time of birth, the levels of donor and patient mtDNA appeared to have stabilised (no further increases were seen at 6 months and one year). All of the children born remain developmentally normal and healthy. Limitations, reasons for caution After using MST, several pregnancies were achieved for patients with a long history of unsuccessful IVF attempts, associated with poor oocyte quality and a failure to produce blastocysts. However, this small pilot study lacked the controls necessary for a definitive evaluation of MST as a tool for infertility treatment. Wider implications of the findings All children born following MST were healthy. However, our results clearly demonstrate that a substantial degree of mtDNA ‘reversal’ is possible. Consequently, mitochondrial replacement therapies used for avoidance of mtDNA disorders might not always be successful, even when initial levels of mutant mtDNA in reconstructed oocytes are very low. Trial registration number ISRCTN11455145

P-473 The reproductive performance of euploid blastocysts declines after each consecutive embryo transfer: The pendulum is swinging back?

Abstract Study question the impact of euploid blastocysts on reproductive performance by association between the number of previous failed IVF cycles and live birth rate per transfer Summary answer Our findings suggest a negative association between the number of previous failed IVF cycles per euploid transfers. implantation rates decreased following each consecutive FE-ET cycles What is known already In assisted reproductive technologies, implantation failure presents a challenging clinical dilemma since its underlying etiology is unknown. Implantation is a very complex process which involves a variety of factors related to the embryo, endometrium, and immune system (Fox et al. 2016). Therefore, implantation failure is also a complex pathological condition that involve both embryonic defects and/or endometrial dysfunctions (Das et al.2012). This situation poses a therapeutic dilemma. Hence implantation failure etiologies and treatments remain unresolved. which results in ongoing debate over whether embryonic chromosomal aneuploidy is a major contributor or within the endometrium itself. Study design, size, duration This observational cohort study included 387 patients undergoing euploid embryo transfer between January 2015 and until October 2022. Participants/materials, setting, methods Participants: Women with an anatomically normal uterus who underwent autologous vitrified-warmed euploid blastocyst transfer (Frozen Euploid Embryo Transfer: FE-ET) cycles were included in the study. Setting: Fertility center at a university-affiliated public hospital. Intervention(s): Trophectoderm biopsy and comprehensive preimplantation 24-chromosome analysis using Next Generation Sequencing (NGS). Main Outcome Measure(s): Cumulative outcomes from these cycles were analyzed. A logistic regression model was used to assess the differences in outcomes between the first, second, and third FE-ET. Main results and the role of chance The mean age of the patient population under investigation was 33.4 ± 5.3 years. Maternal age at oocyte retrieval was negatively associated with the mean euploidy rate per cohort of biopsied blastocysts from each patient (m-ER). The m-ER did not show any association with the number of previous failed IVF cycles (0/1-2/≥3) among different ranges of maternal age at oocyte retrieval (≤30/31-35/36-39/≥40). The transfer of the first single vitrified-warmed euploid blastocyst was associated with an implantation rate (IR) of 47%, a miscarriage rate of 17.9% and a live birth rate (LBR) of 33.9%. Miscarriage rate and LBR were sensitive to the number of previous failed IVF cycles, showing statistically significant differences between women with no previous and ≥3 failed IVF cycles (11.3% versus 27.8%, P = 0.04) and (40.7% versus 26.3%, P = 0.05) respectively. Sustained implantation rates of the first, second, and third FE-ET were 47%, 40.5%, and 30% per transfer, respectively. The sustained IR was sensitive to the number of consecutive euploid blastocyst transfers (P = 0.03). Limitations, reasons for caution The retrospective nature of the study. The data should also be verified using a multicenter approach, to increase the sample size. Wider implications of the findings After experiencing multiple unsuccessful IVF cycles, transferring euploid blastocysts leads to improved clinical outcomes, but these improvements eventually level off. Additional information beyond embryo euploidy is needed to further enhance clinical outcomes. Trial registration number not applicable

Impact of access to care and race/ethnicity on IVF care discontinuation

Research questionIs race/ethnicity or access to care, as defined by insurance coverage, distance to the clinic and zip code (postal code), associated with care discontinuation following IVF? DesignA retrospective cohort study of 878 diverse women who underwent 1571 IVF cycles from 2014 to 2018 at a Southeastern academic medical centre was performed. Women were divided into low (LAC) and high (HAC) access to care groups. HAC was defined as possessing IVF insurance coverage, living ≤25 miles from the clinic, and living in a zip code with a median income ≥$75,000. Access groups and racial/ethnic groups were compared for differences in relative risk of care discontinuation following an unsuccessful IVF cycle. ResultsWomen with HAC had a poorer IVF prognosis than the LAC group, which possibly impacted the association with care discontinuation. Distance to the clinic, but not insurance coverage or zip code, was associated with increased risk of care discontinuation. Among women ≤34 years, HAC showed some evidence of an association with an increased risk of care discontinuation (adjusted relative risk 2.5, 95% confidence interval 0.8–8.1). Despite having higher rates of insurance coverage (51.2% versus 36.5%), non-Hispanic Black women were more likely to discontinue care (58.3% versus 40.2%) and less likely to achieve a live birth (53.0% versus 68.0%) than non-Hispanic White women. ConclusionsIdentification as non-Hispanic Black, and distance to the clinic, but not insurance coverage or zip code, were associated with increased risk of care discontinuation following an unsuccessful IVF cycle. In women ≤34 years old, HAC may be associated with a higher rate of care discontinuation.

EFFECT OF CO-INCUBATION OF SPERMATOZOA WITH HUMAN ENDOMETRIAL CELLS ON ASSISTED REPRODUCTION OUTCOMES

Тo evaluate the effect of the co-incubation of spermatozoa with human endometrial cells prior ICSI on the assisted reproduction outcomes (fertilisation rate, proportion of high quality embryos, implantation rate and live birth rate) in couples with unexplained infertility. Prospective. 110 couples fulfilled the inclusion criteria of unexplained infertility and males with normozoospermia or teratozoospermia. All patients have signed written informed consent. Couples were randomly allocated to study group (n=55) and control group (n=55). After liquefaction all fresh semen samples were washed and were subjected to swim up. Semen samples from the study group were co-incubated for 2 hours with endometrial cell culture, obtained from their partners’ endometrial biopsy. All patients underwent standard ICSI protocol. Embryo transfer was performed in 42 couples of the control group and on 40 couples in the co-incubation group. Main outcomes were fertilisation rate, proportion of high quality embryos, implantation rate and live birth rate. Statistical analyses were performed using SPSS v21. P>0.005 was considered significant. The study group and the control group were comparable in terms of female age, male age, count of unsuccessful IVF cycles, oocyte count and oocyte quality. There were no significant differences in the fertilisation rate (78±9% vs. 80±8%, p>0.05) and the proportion of high quality embryos (62±12% vs. 65±9%, p>0.05) between the co-incubation group and the control group. However, the implantation rate after sperm co-incubation with human endometrial cells was significantly higher when compared to the control group (46% vs. 33%, p<0.05). The live birth rate of the successfully implanted embryos was also significantly higher in the co-incubation group in comparison to the control group (95% vs. 40%, p=0.003). Co-incubation of spermatozoa with endometrial cell culture has no effect on fertilisation rate and proportion of high quality embryos, but leads to higher implantation rate and live birth rate in comparison to conventionally prepared semen for ICSI. These results indicate that couples with unexplained infertility can benefit from sperm co-incubation with endometrial cells before performing ICSI.

Do patient factors influence embryologists' decisions to freeze borderline blastocysts?

To investigate whether patient factors influence the decision to freeze a blastocyst with low implantation potential. This experimental study assessed 170 practicing embryologists from a variety of countries who were recruited via an online survey. Participants were currently practicing embryologists, who grade blastocysts as part of this role. The survey presented decision-making 'vignettes' to participants. These included specific patient information, as well as an image of an expanded blastocyst that was of borderline quality for inner cell mass and trophectoderm, for which the embryologist selected whether or not to freeze. High/low maternal age, the presence/absence of other top quality blastocysts, and the presence/absence of previously unsuccessful IVF cycles were systematically varied within the patient information in a 2 × 2 × 2 design. Participants reported how likely they would be to freeze a particular blastocyst on a scale of 1 (Extremely Unlikely) to 7 (Extremely Likely), and whether or not they would ultimately freeze each blastocyst (Yes or No). Lower maternal age, no other high-quality blastocysts within the cohort, and multiple unsuccessful IVF cycles were associated with greater likelihood of recommending to freeze (P < .001). Furthermore, significant interactions among all three patient factors were noted. This study provides evidence suggesting that when faced with an uncertain blastocyst, factors pertaining to the patient (maternal age, the presence/absence of other top quality blastocysts, and the presence/absence of previously unsuccessful IVF cycles) influence the decision to freeze.

No increased risk of relapse of breast cancer for women who give birth after assisted conception.

STUDY QUESTIONIs childbirth after IVF associated with a risk of relapse in breast cancer?SUMMARY ANSWERWomen who had been diagnosed with breast cancer and completed treatment had no increased risk of relapse if they gave birth after conceiving with IVF.WHAT IS KNOWN ALREADYPregnancy and childbirth have not been shown to increase the risk of relapse in breast cancer. Ovarian stimulation during IVF increases the oestrogen levels and could theoretically increase the risk of relapse in breast cancer.STUDY DESIGN, SIZE, DURATIONThis is a retrospective register study, using national Swedish register data from the National Patient Register, the Medical Birth Register, the Swedish National Cancer Register, the National Breast Cancer Register, the National Quality Registry of Assisted Reproduction (Q-IVF), the National IVF Dataset, the Swedish Prescribed Drug Register and the Cause of Death Register. All women diagnosed with breast cancer who were between 20 and 44 years of age during the years 1982 to 2014 and identified in the cancer registries were assessed.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen, previously diagnosed with breast cancer, who had given birth after IVF (29 after completed breast cancer treatment and 8 after fertility preservation) were compared with a matched control group who had given birth after spontaneous conception. Matching was done in a ratio 1:4, based on T-stage (size of the tumour) and year of diagnosis +/−5 years.MAIN RESULTS AND THE ROLE OF CHANCEWe found 26 114 women that had been diagnosed with breast cancer when 20–44 years old and of those 860 had subsequently given birth, 823 after spontaneous and 37 after IVF conception. Follow-up time was similar between the groups, ranging from 2.6 to 24.0 years, with a mean follow-up time of 10.3 (SD 4.2) years in the IVF group and 10.7 (SD 4.4) years in the control group. There were no relapses (0/37) in the IVF group. The relapse rate for the matched controls was 36/148 (24.8%). Ten women who suffered relapse died due to breast cancer.LIMITATIONS, REASONS FOR CAUTIONThis is reassuring data; however, the result is based on a few cases. The poor coverage of important prognostic variables in the register resulted in uncertain comparability of the groups. The main limitation in this study is the extent of missing data on tumour-related variables, due to poor coverage from the early years of the National Breast Cancer Register. It is possible that the women accepted for IVF had a less aggressive breast cancer and were generally healthier than women delivering after conceiving spontaneously and therefore had a lower risk of relapse. Other limitations are the lack of information on the anticancer therapies used and type of disease relapse, plus the older of the two IVF registers did not hold information on unsuccessful IVF cycles, leaving only cycles leading to birth, to be analysed.WIDER IMPLICATIONS OF THE FINDINGSWe found no indication that women who had been diagnosed with breast cancer had an increased risk of relapse if they gave birth after conceiving with IVF. Based on our findings, there is no evidence to advise against IVF treatment in this group of women. More detailed registry data would be valuable for future studies, enabling proper matching of tumour characteristics between groups.STUDY FUNDING/COMPETING INTEREST(S)The study was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-720291), The Assar Gabrielsson Fund (FB 15-20), The Breast Cancer Fund and the Swedish Association of Local Authorities and Regions, SKL. There are no conflicts of interest to declare.

Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical trial

Does preimplantation genetic testing for aneuploidy (PGT-A) by comprehensive chromosome screening (CCS) of the first and second polar body to select embryos for transfer increase the likelihood of a live birth within 1 year in advanced maternal age women aged 36-40 years planning an ICSI cycle, compared to ICSI without chromosome analysis? PGT-A by CCS in the first and second polar body to select euploid embryos for transfer does not substantially increase the live birth rate in women aged 36-40 years. PGT-A has been used widely to select embryos for transfer in ICSI treatment, with the aim of improving treatment effectiveness. Whether PGT-A improves ICSI outcomes and is beneficial to the patients has remained controversial. This is a multinational, multicentre, pragmatic, randomized clinical trial with intention-to-treat analysis. Of 396 women enroled between June 2012 and December 2016, 205 were allocated to CCS of the first and second polar body (study group) as part of their ICSI treatment cycle and 191 were allocated to ICSI treatment without chromosome screening (control group). Block randomization was performed stratified for centre and age group. Participants and clinicians were blinded at the time of enrolment until the day after intervention. Infertile couples in which the female partner was 36-40 years old and who were scheduled to undergo ICSI treatment were eligible. In those assigned to PGT-A, array comparative genomic hybridization (aCGH) analysis of the first and second polar bodies of the fertilized oocytes was performed using the 24sure array of Illumina. If in the first treatment cycle all oocytes were aneuploid, a second treatment with PB array CGH was offered. Participants in the control arm were planned for ICSI without PGT-A. Main exclusion criteria were three or more previous unsuccessful IVF or ICSI cycles, three or more clinical miscarriages, poor response or low ovarian reserve. The primary outcome was the cumulative live birth rate after fresh or frozen embryo transfer recorded over 1 year after the start of the intervention. Of the 205 participants in the chromosome screening group, 50 (24%) had a live birth with intervention within 1 year, compared to 45 of the 191 in the group without intervention (24%), a difference of 0.83% (95% CI: -7.60 to 9.18%). There were significantly fewer participants in the chromosome screening group with a transfer (relative risk (RR) = 0.81; 95% CI: 0.74-0.89) and fewer with a miscarriage (RR = 0.48; 95% CI: 0.26-0.90). The targeted sample size was not reached because of suboptimal recruitment; however, the included sample allowed a 90% power to detect the targeted increase. Cumulative outcome data were limited to 1 year. Only 11 patients out of 32 with exclusively aneuploid results underwent a second treatment cycle in the chromosome screening group. The observation that the similarity in birth rates was achieved with fewer transfers, less cryopreservation and fewer miscarriages points to a clinical benefit of PGT-A, and this form of embryo selection may, therefore, be considered to minimize the number of interventions while producing comparable outcomes. Whether these benefits outweigh drawbacks such as the cost for the patient, the higher workload for the IVF lab and the potential effect on the children born after prolonged culture and/or cryopreservation remains to be shown. This study was funded by the European Society of Human Reproduction and Embryology. Illumina provided microarrays and other consumables necessary for aCGH testing of polar bodies. M.B.'s institution (UZBrussel) has received educational grants from IBSA, Ferring, Organon, Schering-Plough, Merck and Merck Belgium. M.B. has received consultancy and speakers' fees from Organon, Serono Symposia and Merck. G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, IBSA, Glycotope, Abbott and Gedeon-Richter as well as personal fees from VitroLife, NMC Healthcare, ReprodWissen, BioSilu and ZIVA. W.V., C.S., P.M.B., V.G., G.A., M.D., T.E.G., L.G., G.Ka., G.Ko., J.L., M.C.M., M.P., A.S., M.T., K.V., J.G. and K.S. declare no conflict of interest. NCT01532284. 7 February 2012. 25 June 2012.

Can a quality-of-life assessment assist in identifying women at risk of prematurely discontinuing IVF treatment? A prospective cohort study utilizing the FertiQoL questionnaire.

This study aimed at assessing quality of life (QoL) by means of a validated measurement tool (FertiQoL) in German infertile patients before a first IVF/ICSI cycle with ancillary assessment of changes in FertiQoL scores after a failed first cycle and the predictive capacity of FertiQoL scores for treatment discontinuation. The validated FertiQoL tool consisting of 24 questions regarding fertility-specific aspects of QoL was used for this prospective cohort study conducted at a university affiliated IVF center in Germany. Female patients (n = 119) filled out the FertiQoL form and questionnaire on sociodemographic variables on initiation of a first- and second-cycle IVF/ICSI treatment, respectively. On initiation of a first IVF/ICSI cycle, the mean scores (± standard deviation) for subscales emotional, mind-body, relational, and social items were 62 (± 19), 75 (± 17), 82 (± 13), and 78 (± 14), respectively; the total FertiQoL score was 73 (± 12). The mean total FertiQoL score at initiation of a first treatment cycle did not differ between patients who continued vs. discontinued treatment in case of no pregnancy achievement in the first cycle (73) (± 10) vs. 74 (± 14), p = 0.46). Furthermore, the mean total FertiQoL score did not change after an unsuccessful first IVF cycle (74 vs. 76, p = 0.46). There was no statistical difference in a small sample size for FertiQoL scores between all groups. In this study, FertiQoL scores were, therefore, not usable to predict withdrawal from infertility treatment.

Clinical and Anamnestic, Immunological, Echographic, and Hysteroscopic Features of Chronic Endometritis Associated with Impaired Reproductive Function

Background: The widespread prevalence of infertility, the low effectiveness of assisted reproductive technologies (ART), and the high incidence of chronic endometritis (CE) in infertile women determine the relevance of the considered problem. The aim of the study was to determine the clinical and anamnestic, laboratory, and instrumental features of CE associated with infertility and unsuccessful IVF cycles in women of reproductive age. Materials and methods: The study enrollred 150 women of reproductive age with morphologically established CE (main group, n=120) and without CE (control group, n=30). A subgroup I of the main group included 64 patients with infertility and IVF failures, a subgroup II – 56 fertile women. In addition to anamnesis collection and identification of CE clinical features, all patients underwent infectious screening, immunological and immunohistochemical analysis, ultrasound examination of pelvic organs with dopplerometry, and office hysteroscopy. A comparative analysis of the data obtained from subgroups of the main group was conducted. Results: Histological study of endometrial pipelle-biopsy specimens on the 7−10th day of the cycle revealed CE in all patients of the main group. We found prevalence of mean duration of CE in the subgroup I relative to subgroup II ― 5.5±0.06 years and 2.4±0.07 years, respectively (p0.001). Infectious screening showed that 58 (90.6%) patients of the I subgroup had sterile endometrial seeding which was 16.9 times higher than in subgroup II (p0.0001). Immunological analysis determined the presence of AEAT in all patients of the subgroup I, 43 of which (67.2%) were above 265 U/ml, while 51 (91.1%) of subgroup II had no AEAT (p0.001). Immunohistochemical analysis of the endometrium on the 18th−24th day of the cycle established high expression of CD16 , CD20 , CD56 , and HLA-DRII in 58 (90.6%) patients of the subgroup I, whereas in 54 patients (96.4%) of II subgroup high expression of CD16 and CD20 with low amount of CD56- and HLA-DRII-positive cells was registered (p0.001). We determined prognostically significant clinical and anamnestic risk factors predisposing to the development of infertility in patients with CE (p0,05). We revealed certain echographic, dopplerometric, and hysteroscopic criteria of CE demonstrating the critical disruption of endometrial receptivity in infertile women. Conclusion: Most patients (90.6%) with infertility had autoimmune component of CE characterized by prolonged (more than 5 years) course, high serum level of AEAT, sterile endometrial crops, and high expression of inflammation markers CD16 , CD20 , CD56 and HLA-DRII .

A longitudinal study investigating the role of decisional conflicts and regret and short-term psychological adjustment after IVF treatment failure.

What is the relationship between decisional conflict, decisional regret and psychological well-being in women following unsuccessful IVF cycles? The mediating effect of decisional regret on the relationship between decisional conflict and fertility-related quality of life (FRQOL) has been found to be moderated by the availability (versus absence) of frozen embryos after an unsuccessful IVF cycle. Infertility treatment is marked by its open-ended nature. Stresses in treatment decision-making could be aggravated by a culture which honours families through procreation. While studies have investigated treatment-related decision-making among infertile women, little is known about the mental health consequences of decisional conflict and decisional regret following an unsuccessful IVF cycle. A study was conducted over a 3-month period with infertile women who had recently experienced a failed IVF cycle (T0). Decisional conflict when they decided on terminating or continuing treatment (T1) and decisional regret 3 months later (T2) were measured. Participants reported their levels of depression, anxiety and FRQOL at three time points. A total of 151 participants completed all time points (attrition rate: 39%). The average age of participants was 37.2 years, and they had had 1.1 cycles (range: 0-8) on average at the time of study intake. The duration of the study was 2 years. Participants were infertile women who were not pregnant following an IVF cycle recruited from a university-affiliated assisted reproduction centre. Following the notification of a negative pregnancy result, patients were invited to complete measures of FRQOL, depression and anxiety across three time points and decisional conflict and decisional regret at T1 and T2 respectively. Decisional regret partially mediated the effect of decisional conflict on overall and treatment-specific FRQOL (P<0.05). The mediation by decisional regret was present only among participants who had no remaining frozen embryos after their unsuccessful IVF cycle (P<0.05). Self-selection bias at recruitment remains a concern. Our results show for the first time how mental health implications of decisional conflict may vary among patients with different clinical characteristics (i.e. availability of frozen embryos), despite their common experience of an unsuccessful IVF cycle. Healthcare professionals should be aware of the psychological ramifications of treatment decision-making difficulties, as well as individual differences in adjustment to unsuccessful treatment. The study was funded by the Hong Kong University Grant Council-General Research Fund (HKU740613) and the authors have no conflicts of interest. HKU Clinical Trials Registry (Trial registration number: HKUCTR-1680).

Endometrial receptivity assessment and personalized patient care management: a mean to optimize pregnancy rate

The aim of this study was to optimize pregnancy outcome using personalized care management by combining embryo replacement according to the evaluation of endometrial receptivity in patients with multiple implantation failure after several unsuccessful IVF cycles awaiting for transfer of cryopreserved embryos under hormonal substitution treatment (HST) or natural cycle.

Understanding reproducibility of human IVF traits to predict next IVF cycle outcome.

Evaluating the failed IVF cycle often provides useful prognostic information. Before undergoing another attempt, patients experiencing an unsuccessful IVF cycle frequently request information about the probability of future success. Here, we introduced the concept of reproducibility and formulae to predict the next IVF cycle outcome. The experimental design was based on the retrospective review of IVF cycle data from 2006 to 2013 in two different IVF centers and statistical analysis. The reproducibility coefficients (r) of IVF traits including number of oocytes retrieved, oocyte maturity, fertilization, embryo quality and pregnancy were estimated using the interclass correlation coefficient between the repeated IVF cycle measurements for the same patient by variance component analysis. The formulae were designed to predict next IVF cycle outcome. The number of oocytes retrieved from patients and their fertilization rate had the highest reproducibility coefficients (r = 0.81 ~ 0.84), which indicated a very close correlation between the first retrieval cycle and subsequent IVF cycles. Oocyte maturity and number of top quality embryos had middle level reproducibility (r = 0.38 ~ 0.76) and pregnancy rate had a relative lower reproducibility (r = 0.23 ~ 0.27). Based on these parameters, the next outcome for these IVF traits might be accurately predicted by the designed formulae. The introduction of the concept of reproducibility to our human IVF program allows us to predict future IVF cycle outcomes. The traits of oocyte numbers retrieved, oocyte maturity, fertilization, and top quality embryos had higher or middle reproducibility, which provides a basis for accurate prediction of future IVF outcomes. Based on this prediction, physicians may counsel their patients or change patient's stimulation plans, and laboratory embryologists may improve their IVF techniques accordingly.

Effect of in vitro culture period on birthweight of singleton newborns

Does prolonged in vitro culture influence newborn birthweight? The absolute mean birthweight and gestational age- and gender-adjusted birthweight (Z scores) of singletons born from blastocyst transfer are higher than singletons born from Day 3 transfer. An increased proportion of large-for-gestational age (LGA) newborns occurs after blastocyst transfer compared with Day 2 transfer, and Z scores for newborns after blastocyst transfer are higher than newborns after transfer on Day 2 or Day 3. This study was a retrospective analysis of newborn birthweight, including 2929 singletons at the Reproductive Medical Center of Peking University Third Hospital between January 2009 and June 2012. The number of singletons after Day 3 transfer was 2833 and the number of singletons after blastocyst transfer (Day 5-6) was 96. Only cycles with fresh embryo transfer were included. Patients ≤40 years of age with a BMI < 30 kg/m(2) were analyzed. Only data from singleton newborns born alive after the 20th week of gestation were included in the data analysis. Patients with more than one fetal sac diagnosed by ultrasound but who delivered singletons were excluded. Patients who received PGD and cycles with donor oocytes were excluded. Multiple linear regression analysis was performed to determine the significance of individual factors on absolute birthweight of singleton newborns. The absolute birthweight and Z scores of singletons were compared. Multiple linear regression analysis indicated that maternal age, maternal BMI, paternal BMI, type of infertility, gestational age, infant gender and culture period were significantly associated with birthweight. The absolute birthweight for singletons resulting from blastocyst transfer was significantly greater than singletons resulting from Day 3 transfer (3465.31 ± 51.36 versus 3319.82 ± 10.04 g respectively, P = 0.009). The Z scores for singletons after blastocyst transfer were significantly higher than singletons after Day 3 transfer (0.347 versus 0.029 respectively, P = 0.016). In our clinic, blastocyst culture is mainly offered to patients with unsuccessful IVF cycles but also to patients with uterine malformations, and therefore this protocol introduced a potential selection bias in our study. Moreover, as certain culture media are associated with fetal overgrowth, the media used may be also a confounding factor, even though the absolute birthweights of singletons were comparable. Our study suggests that a prolonged (5-6 days) in vitro culture period has a significant effect on the mean absolute birthweight and Z scores of singleton newborns. The effect of prolonged in vitro culture on epigenetic changes in the embryo needs further study. National Natural Science Foundation of China for Young Scholars (81300483). The authors have no conflicts of interest to declare. Not applicable.

Endometrial Scratch-Suction and Implantation Failure

Objective: The aim of this trial was to determine whether endometrial scratch-suction caused by insertion tube of (IUCD) with suction improved the probability of pregnancy in the subsequent IVF cycle in patients who had previous failed IVF outcome by removing small polyps and any hazardous materials. Design: Observational prospective cohort experimental study. Setting: Zagazig University Hospital, Obstetrics and Gynecology department. From period between September 2011 till September 2012. Population: 30 patients with previous failed IVF despite transfer of goodquality embryos were allocated to endometrial scratch-suction in the same the cycle of embryo transfer. Methods: From day 5 to day 7 of same ICSI cycle, the patients in study underwent endometrial scratch-suction technique. After preparation of insertion tube of (IUCD) and infant feeding tube 8 F, moving the insertion tube of IUCD from below upwards with scratching anterior uterine wall, then posterior, then left lateral uterine wall, then right lateral uterine wall, then fundus, all these steps are associated with suction by attaching proximal end of infant feeding tube 8 F to suction apparatus. Main Outcome Measures: Implantation and clinical pregnancy rates. Results: The implantation occurred in 24/30 (80%). The clinical pregnancy occurred in 20/30 patients (66.66%). 12/30 patients (40%) during scratch-suction technique had small fleshy masses obstructing suction tube which were small endometrial polyps. Conclusions: Endometrial scratch-suction improves clinical pregnancy and implantation rates in the same IVF-ET cycle in patients with previous unsuccessful IVF cycles.

Medical factors associated with early IVF discontinuation

Even when IVF is reimbursed by the social insurance system, as in France, high discontinuation rates have been reported and some patients drop out as soon as the first failed IVF cycle. This study aims to investigate medical factors associated with treatment discontinuation in an IVF centre after the first unsuccessful cycle. The study included 5135 couples recruited in eight French IVF centres and who had had an unsuccessful first IVF cycle in these centres in 2000–2002 (i.e. no live birth). Of these couples with a first failed IVF, 1337 did not have a second IVF in the centre (26%, ‘early discontinuation group’) and 3798 continued treatment with a second IVF in the centre. The characteristics of couples who discontinued IVF treatment were compared with those who continued using logistic regressions. Older women, women with duration of infertility >5years, with female factor or unexplained infertility, with 0 or 1 oocyte retrieved and no embryo transfer during the first IVF were more likely to discontinue treatment early. Risk of early discontinuation was associated with medical factors that are also well known to be associated with impaired chance of successful IVF.Even when IVF is reimbursed by the social insurance system, as in France, high discontinuation rates have been reported and some patients drop out as soon as the first failed IVF cycle. This study aims to investigate medical factors associated with treatment discontinuation in an IVF centre after the first unsuccessful cycle. The study included 5135 couples recruited in eight French IVF centres who had had an unsuccessful first IVF cycle in these centres in 2000–2002 (i.e. who remained childless after a first cycle). Of these couples with a first failed IVF, 1337 did not have a second IVF in the centre and 3798 continued treatment with a second IVF in the centre. The characteristics of couples who discontinued IVF treatment were compared with those who continued. After a first failed IVF cycle, more than one-quarter (26%) of couples discontinued IVF treatment. Older women, women with duration of infertility >5years, with female factor or unexplained infertility, with 0 or 1 oocyte retrieved and with no embryo transfer during the first IVF were more likely to discontinue treatment early. The risk of early discontinuation was associated with medical factors that are also well known to be associated with impaired chance of success during IVF treatment. A next step would be to examine whether the early discontinuation results from a decision of the couple themselves, from medical, psychological and/or social staff counselling or from some combination of all of these factors.

Aspirin and heparin as adjuvants during IVF do not improve live birth rates in unexplained implantation failure

This study tested the hypothesis that using aspirin and/or heparin as adjuvants in IVF improves the treatment outcome. This retrospective cohort–control study recruited 234 consecutive subjects aged ⩽44years who had previously had one or more unsuccessful IVF cycle. All underwent IVF using conventional protocols. The study group received aspirin and/or heparin post embryo transfer until the day of pregnancy test or until 12weeks of pregnancy. The control group did not receive adjuvant treatment. The outcome measures were live birth, clinical pregnancy and miscarriage rates. The outcomes were compared by chi-squared test and relative-risk analysis. Analysis was performed in 206 subjects. There was no statistically significant difference in the live birth rate (35.0%, 36/103 versus 47.6%, 49/103), clinical pregnancy rate (40.8%, 42/103 versus 53.4%, 55/103) and miscarriage rate (14.3%, 6/42 versus 10.9%, 6/55) between the study group and the control group. The data in this study show that low-dose aspirin and/or heparin as adjuvant therapies during IVF do not improve live birth rates in an unselected group of subfertile women who have previously had one or more unexplained implantation failure following IVF.This retrospective study examined whether using aspirin and/or heparin during IVF treatment improves the treatment outcomes. A total of 234 women aged ⩽44years who had previously undergone at least one unsuccessful IVF cycle were recruited into the study. All women underwent IVF treatment. The study group received aspirin and/or heparin from the day of embryo transfer until the day of the pregnancy test or until 12weeks of pregnancy, if pregnant. The control group did not receive aspirin and/or heparin. There were no differences in the live birth rates (35%, 36/103 versus 48%, 49/103), clinical pregnancy rates (41%, 42/103 versus 53%, 55/103) and miscarriage rates (14.3%, 6/42 versus 10.9%, 6/55) between the study group and the control group. The data in this study show that low-dose aspirin and/or heparin treatment during IVF does not improve the live birth rate or reduce the miscarriage rate in women who have had previous unsuccessful IVF treatment and whose immunological status is not known.

IVF policies with emphasis on Israeli practices

The social acceptance of IVF has had the effect of shifting the focus of discussion from the earlier disapproval of IVF to its [un]availability. It has also been suggested that affordable ARTs may stop the falling rates of population turnover in Europe. As many couples cannot afford it, let alone in developing countries, there are ongoing efforts to make IVF 'cheaper' and 'affordable'. This paper reviews IVF policies in several countries before focusing particularly on the exceptional policy of the ARTs in Israel. It analyses the effectiveness of IVF cycles over time as reflected in the literature; examines women's health and welfare after long-term IVF use; and asks whether in a scheme of unlimited free-access to IVF, women would necessarily be better off. Review of the literature dealing with IVF outcomes, policies and practices. Long-term effectiveness with IVF is unclear. Age and the number of unsuccessful IVF cycles are predictive of a negative outcome, which is at odds with the Israeli policy of open-ended rounds. Women's health and welfare after long-term IVF remains unclear. In a scheme of unlimited free-access to IVF--in a pro-natalist country--women may end up worse-off. A systematic long-term assessment of the health and welfare of the women after IVF--especially after prolonged treatment with IVF--is necessary to develop a reliable, effective and evidence-based policy on assisted reproduction not only in Israel, but also in other countries.

Successful birth following transfer of frozen–thawed embryos produced from in-vitro matured oocytes

It is well established that ovarian hyperstimulation syndrome (OHSS) is more frequent in patients with polycystic ovarian syndrome. In-vitro maturation (IVM) of immature oocytes presents a potential alternative for the fertility treatment and prevention of OHSS for these patients. This report describes the case of a 26-year old woman with a successful pregnancy and delivery following the transfer of frozen-thawed embryos derived from in-vitro matured oocytes. She had three failed cycles of ovarian stimulation (using low-dose step-up gonadotrophin protocol) with or without intrauterine insemination cycles, an ovulation-induction cycle with luteal long protocol, two fresh IVM cycle and one frozen-thawed IVM cycle. During the IVF cycle, she developed moderate OHSS and required hospitalization for 3 weeks. Following four unsuccessful IVF or IVM cycles, 15 months after the last cryopreservation, six fertilized oocytes were thawed for a scheduled embryo transfer. Following thawing, four fertilized oocytes survived and cleaved. Four frozen-thawed embryos were transferred. Six weeks after embryo transfer an ongoing intrauterine single pregnancy with fetal heartbeat was confirmed by transvaginal ultrasound. An uneventful pregnancy and delivery via Caesarean section at 39 weeks resulted in the birth of a normal healthy infant.

Does local endometrial injury in the nontransfer cycle improve the IVF-ET outcome in the subsequent cycle in patients with previous unsuccessful IVF? A randomized controlled pilot study

BACKGROUND:Management of repeated implantation failure despite transfer of good-quality embryos still remains a dilemma for ART specialists. Scrapping of endometrium in the nontransfer cycle has been shown to improve the pregnancy rate in the subsequent IVF/ET cycle in recent studies.AIM:The objective of this randomized controlled trial (RCT) was to determine whether endometrial injury caused by Pipelle sampling in the nontransfer cycle could improve the probability of pregnancy in the subsequent IVF cycle in patients who had previous failed IVF outcome.SETTING:Tertiary assisted conception center.DESIGN:Randomized controlled study.MATERIALS AND METHODS:100 eligible patients with previous failed IVF despite transfer of good-quality embryos were randomly allocated to the intervention group and control groups. In the intervention group, Pipelle endometrial sampling was done twice: One in the follicular phase and again in the luteal phase in the cycle preceding the embryo transfer cycle.OUTCOME MEASURE:The primary outcome measure was live birth rate. The secondary outcome measures were implantation and clinical pregnancy rates.RESULTS:The live birth rate was significantly higher in the intervention group compared to control group (22.4% and 9.8% P = 0.04). The clinical pregnancy rate in the intervention group was 32.7%, while that in the control group was 13.7%, which was also statistically significant (P = 0.01). The implantation rate was significantly higher in the intervention group as compared to controls (13.07% vs 7.1% P = 0.04).CONCLUSIONS:Endometrial injury in nontransfer cycle improves the live birth rate, clinical pregnancy and implantation rates in the subsequent IVF-ET cycle in patients with previous unsuccessful IVF cycles.