Low progesterone levels on the day before natural cycle frozen embryo transfer are negatively associated with live birth rates.

STUDY QUESTION: Are progesterone (P) levels on the day before natural cycle frozen embryo transfer (NC-FET) associated with live birth rate (LBR)? SUMMARY ANSWER: Regular ovulatory women undergoing NC-FET with serum P levels <10 ng/ml on the day before blastocyst transfer have a significantly lower LBR than those with serum P levels >10 ng/ml. WHAT IS KNOWN ALREADY: The importance of serum P levels around the time of embryo transfer in patients undergoing FET under artificial endometrial preparation has been well established. However, no study has analyzed the importance of serum P levels in patients undergoing FET under a true natural endometrial preparation cycle. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study including 294 frozen blastocyst transfers under natural cycle endometrial preparation at a university-affiliated fertility centre between January 2016 and January 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients had regular menstrual cycles and underwent NC-FET with their own oocytes. Only patients who had undergone serum P measurement between 8 am and 11 am on the day before FET were included. Patients did not receive any external medication for endometrial preparation or luteal phase support. Patients were divided into two groups according to serum P levels below or above 10 ng/ml on the day before FET. Univariate analysis was carried out to describe and compare the cycle characteristics with reproductive outcomes. To evaluate the effect of P, a multivariable logistic model was fitted for each outcome after adjusting for confounding variables. MAIN RESULTS AND THE ROLE OF CHANCE: Mean serum P levels on the day before FET were significantly higher in patients who had a live birth compared to those who did not (14.5 ± 7.0 vs 12.0 ± 6.6 ng/ml, 95% CI [0.83; 4.12]). The overall clinical pregnancy rate (CPR) and LBR were 42.9% and 35.4%, respectively. Patients in the higher P group (>10 ng/ml) had a higher LBR (41.1% vs 25.7%: risk difference (RD) 15.4%, 95% CI [5; 26]) and CPR (48.6% vs 33.0%: RD 15.6%, 95% CI [4; 27]). Patients with higher serum P levels on the day before FET (63% of patients) had an improved LBR (odds ratio: 1.05; 95% CI [1.02; 1.09]). Women with serum P levels <10 ng/ml on the day before FET (37% of patients) had significantly higher weights (62.5 ± 9.9 vs 58.1 ± 7.1 kg, 95% CI [1.92; 6.90]) and BMI (22.9 ± 3.6 vs 21.6 ± 2.7 kg/m2, 95% CI [0.42; 2.25]) compared to patients with P levels >10 ng/ml. LIMITATIONS, REASONS FOR CAUTION: The main limitation of our study is its retrospective design. Other potential limitations are the detection of LH surge through urine testing and the inclusion of patients who did and did not undergo preimplantation genetic testing for aneuploidies. The protocol used in our institution for monitoring NC-FET does not look for the onset of progesterone secretion by the corpus luteum, and a slow luteinisation process or delay of corpus luteum function cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS: We provide evidence that a minimum serum P threshold (P >10 ng/ml) might be required for improved reproductive outcomes in NC-FET. This result suggests that there are different mechanisms by which P is produced and/or distributed by each patient. This study also provides an excellent model to evaluate the impact of luteal phase defect through NC-FET. A prospective evaluation to assess whether P supplementation should be individualised according to patient's needs is necessary to support our findings. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used, and there are no competing interests.

Does LH suppression by progesterone-primed ovarian stimulation compared with GnRH antagonist affect live birth rate among oocyte recipients?

RESEARCH QUESTION: Is live birth rate among recipients of donated oocytes different depending on mode of treatment for endogenous LH suppression administered to oocyte donors during ovarian stimulation? DESIGN: A retrospective cohort study of recipients of freshly donated oocytes from oocyte donors who underwent ovarian stimulation with gonadotrophins at a private, university-based infertility clinic between January 2017 and March 2018. For endogenous LH suppression, oocyte donors received daily injections of gonadotrophin releasing hormone antagonist ganirelix (GNR) or daily oral 75 µg desogestrel (DSG) until triggering with 0.2 mg of triptorelin. Three hundred recipient cycles of freshly donated oocytes were included: 154 from oocyte donor DSG cycles and 146 from oocyte donor GNR cycles. RESULTS: Comparison of basal characteristics of oocyte donors showed no differences in mean age, anti-Müllerian hormone levels and body mass index between the oocyte donor DSG p and oocyte donor GNR groups, respectively. Similarly, no differences were observed among mean age of recipients and body mass index. Out of 300 fresh embryo transfers, 190 clinical pregnancies (63.3%) and 150 live births (50%) were achieved. Per embryo transfer clinical pregnancy rate was 66.2% in the DSG recipient group and 60.3% in the GNR recipient group (P = 0.338). Live birth rates were not significantly different between both groups (48.7% among DSG recipient group and 51.4% among GNR recipient group; P = 0.729). CONCLUSIONS: Live birth rate among recipients of donated oocytes does not differ depending on the mode of treatment for endogenous LH suppression administered to the oocyte donors during ovarian stimulation. This information is reassuring and will be of interest to teams using these kinds of protocols, although further research is needed.

Do ovarian endometriomas affect ovarian response to ovarian stimulation for IVF/ICSI?

RESEARCH QUESTION: Does the presence of ovarian endometriomas affect ovarian response to ovarian stimulation after adjusting for age and ovarian reserve markers? DESIGN: This retrospective cross-sectional study compared the ovarian response between patients with ovarian endometriomas and women with other infertility factors undergoing their first ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI). An age-specific nomogram model for the number of oocytes retrieved was built for both groups, and ovarian response was compared after adjusting for age, gonadotrophin dose, anti-Mullerian hormone (AMH) concentration and antral follicle count (AFC). RESULTS: A total of 923 patients were included: 101 women with at least one ovarian endometrioma, and 822 patients with other infertility factors. Comparisons of the nomograms for the number of oocytes retrieved demonstrated that response was significantly lower for women with endometrioma when the results were adjusted for age the z-score for the number of oocytes retrieved (-0.49 ± 0.71 versus -0.20 ± 0.86; 95% confidence interval [CI] -0.47 to -0.12) and also after adjustment for the total dose of gonadotrophins and AMH values (z-score mean difference -0.338; 95% CI -0.54, -0.14). When the z-score was adjusted for gonadotrophin dose and AFC, the number of oocytes retrieved was comparable between the two groups (z-score mean difference -0.038; 95% CI -0.34 to 0.27). CONCLUSIONS: Ovarian response after ovarian stimulation for IVF/ICSI in women with endometriomas is significantly lower than in controls after adjusting for age, gonadotrophin dose and AMH. Dose and protocol selection for ovarian stimulation in patients with endometrioma should be based on AFC rather than AMH, as the latter may be overestimated.

Effect of embryo transfer difficulty on live birth rates studied in vitrified-warmed euploid blastocyst transfers.

RESEARCH QUESTION: The aim of this study was to investigate the relationship between the different manoeuvres employed or degrees of difficulty during embryo transfer and live birth rate (LBR) in frozen euploid (blastocyst) embryo transfer (FEET). DESIGN: A retrospective, observational study of women undergoing FEET was performed. If the catheter encountered any resistance in its passage through the cervix, a stepwise approach was used. Easy embryo transfer was defined as a direct embryo transfer or use of the outer sheath of the catheter. Difficult embryo transfer was defined as when the process required the use of a Wallace Malleable Stylet (Smiths Medical International Ltd., UK) without or with additional instrumentation such as a tenaculum or uterine sound. RESULTS: The analysis involved 370 FEET. LBR was significantly lower in difficult FEET procedures compared with easy ones (54.5% versus 40.5%, P = 0.026) but significance was lost after adjustment for confounders. Use of the outer sheath use did not affect LBR. Although LBR was significantly lower when the stylet, without or with a tenaculum, was required (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.34-0.93; P < 0.05), no statistically significant reduction was observed after adjustment for confounders (OR 0.81, 95% CI 0.45-1.47). CONCLUSIONS: No significant reduction in LBR was observed after adjustment for confounders between difficult and easy FEET, or when use of stylet without or with a tenaculum was required for embryo transfer. The lack of significance may be due to factors such as the sample size or the use of array comparative genomic hybridization analysis. Further studies are needed to confirm these results.

Deconstructing the myth of poor prognosis for fast-cleaving embryos on day 3. Is it time to change the consensus?

PURPOSE: To determine the developmental competence of fast-cleaving D3 embryos. METHODS: Retrospective study including 4028 embryos from 513 PGT-A cycles performed between July 2014 and June 2017. Embryos were cultured in time-lapse incubators and biopsied at blastocyst stage. Embryos were classified in groups according to the number of cells on D3 (from 2-cell to ≥13 -cell and compacted). A generalized linear mixed model adjusted for confounding factors was performed to assess the chance to give rise to an euploid blastocyst in each group compared with the chance of 8-cell embryos. Implantation and live birth rates were also analyzed. RESULTS: The statistical analysis showed that embryos with 9 to 11 cells had a slightly lower euploid blastocyst rate than 8-cell embryos (OR (95% CI) 0.77 (0.61-0.96)) while embryos with more than 11 cells were found to be just as likely to give rise to an euploid blastocyst as the 8-cell embryos (OR (95% CI) 1.20 (0.92-1.56)). Conversely, slow-cleaving embryos had a significantly lower euploid blastocyst rate than 8-cell embryos (OR (95% CI) 0.31 (0.24-0.39)). Moreover, euploid blastocysts derived from fast-cleaving embryos and from 8-cell embryos exhibit similar live birth rates. No significant differences were found in the chance to give rise a live birth between 8-cell and 9- to 11-cell embryos (OR (95% CI) 1.23 (0.70-2.15)) and > 11-cell embryos (OR (95% CI) 1.09 (0.57-2.09)). CONCLUSIONS: Embryos with more than 11 cells exhibit similar developmental competence to 8-cell embryos. Their poor prognosis should be reconsidered.

Reproductive outcomes in recipients are not associated with oocyte donor body mass index up to 28 kg/m2: a cohort study of 2722 cycles.

The effect of increasing donor body mass index (BMI) on clinical pregnancies was retrospectively analysed in a cohort of consecutive 2722 donor oocyte IVF cycles. The relationship between donor BMI and clinical pregnancies was assessed after adjusting for recipient BMI. Clinical pregnancy rates and live birth rates (LBR) were no different with increasing donor BMI (up to donor BMI ≤28 kg/m2). The odds of pregnancy did not vary with donor BMI. Compared with donor BMI quartile 1, OR 95% CI of clinical pregnancy was 1.01 (0.82 to 1.25), 1.01 (0.82 to 1.25) and 0.90 (0.73 to 1.12) for quartiles 2, 3 and 4 respectively. A statistically significant reduction of cumulative LBR (P = 0.036) and LBR (P = 0.011) was observed in the results of donation cycles according to recipient BMI quartiles. A reduced odds of clinical pregnancy was observed with increasing recipient BMI. Compared with recipient BMI quartile 1, OR 95% CI of clinical pregnancy was 0.84 (0.68 to 1.03), 0.79 (0.63 to 00.97) and 0.78 (0.63 to 0.971) for quartiles 2, 3 and 4, respectively. A negative effect on oocyte donation cycle outcomes with increased donor BMI was not found after adjusting oocyte donor and recipient BMI.

Selecting embryos with the highest implantation potential using data mining and decision tree based on classical embryo morphology and morphokinetics.

PURPOSE: The objective of this work was to determine which embryonic morphokinetic parameters up to D3 of in vitro development have predictive value for implantation for the selection of embryos for transfer in clinical practice based upon information generated from embryo transfers with known implantation data (KID). METHODS: A total of 800 KID embryos (100% implantation rate (IR) per transfer and 0% IR per transfer) cultured in an incubator with Time-Lapse system were retrospectively analysed. Of them, 140 embryos implanted, whereas 660 did not. RESULTS: The analysis of morphokinetic parameters, together with the embryo morphology assessment on D3, enabled us to develop a hierarchical model that places the classical morphological score, the t4 and t8 morphokinetic values, as the variables with the best prognosis of implantation. CONCLUSION: In our decision tree, the classical morphological score is the most predictive parameter. Among embryos with better morphological scores, morphokinetics permits deselection of embryos with the lowest implantation potential.

NGS-Based Assay for the Identification of Individuals Carrying Recessive Genetic Mutations in Reproductive Medicine.

Next-generation sequencing (NGS) has the capacity of carrier screening in gamete donation (GD) programs. We have developed and validated an NGS carrier-screening test (qCarrier test) that includes 200 genes associated with 368 disorders (277 autosomal recessive and 37 X-linked). Carrier screening is performed on oocyte donation candidates and the male partner of oocyte recipient. Carriers of X-linked conditions are excluded from the GD program, whereas donors are chosen who do not carry mutations for the same gene/disease as the recipients. The validation phase showed a high sensitivity (>99% sensitivity) detecting all single-nucleotide variants, 13 indels, and 25 copy-number variants included in the validation set. A total of 1,301 individuals were analysed with the qCarrier test, including 483 candidate oocyte donors and 635 receptor couples, 105 females receiving sperm donation, and 39 couples seeking pregnancy. We identified 56% of individuals who are carriers for at least one genetic condition and 1.7% of female donors who were excluded from the program due to a carrier state of X-linked conditions. Globally, 3% of a priori assigned donations had a high reproductive risk that could be minimized after testing. Genetic counselling at different stages is essential for helping to facilitate a successful and healthy pregnancy.

Investigations into implantation failure in oocyte-donation recipients.

In recent decades, the Western world has been experiencing a societal trend to prioritize the professional careers of women who postpone motherhood to about 40 years of age, when, unfortunately, natural reproductive potential declines. This is the reason why these women increasingly find it necessary to resort to oocyte donation to have a child. Thanks to the young age of the donors, the efficacy of oocyte donation is the highest of all assisted reproduction treatments and pregnancy rates achieved with this technique exceed 50%. Moreover, the large registries from ESHRE and ASRM show live birth rates close to this figure. However, there are patients who experience repeated failures in several oocyte-donation cycles, and so far oocyte-donation repeated implantation failure has not been clearly defined. This study analysed the results obtained from 2531 oocyte-donation cycles carried out in 1990 patients and defines oocyte-donation repeated implantation failure as failure to implant with more than two embryo transfers and more than four high-grade embryos transferred. This study observed this condition in 140 oocyte recipients (7%). Also, oocyte cohort size, uterine factors and systemic thrombophilias as important aetiological factors were identified were to offer new therapeutic strategies to patients.

Live birth using vitrified--warmed oocytes in invasive ovarian cancer: case report and literature review.

This article reports the live birth of a healthy newborn using vitrified-warmed oocytes in a young patient with invasive mucinous ovarian carcinoma (stage Ic). Diagnosis was performed after a laparoscopic left adnexectomy. She underwent two cycles of ovarian stimulation, and 14 oocytes were vitrified before fertility-sparing surgery with uterus preservation went ahead. One year later, a transfer of two embryos was performed after insemination of warmed oocytes. Eighteen days after the transfer, she underwent a laparotomy because of abdominal pain, vaginal bleeding and haemoperitoneum. A right cornual ectopic pregnancy in the uterus was diagnosed and a wedge resection was performed to resolve it. One week later, a viable intrauterine pregnancy was confirmed under ultrasound. An elective Caesarean section was performed at week 38 of gestation, resulting in the birth of a healthy boy weighing 2650 g. As far as is known, this is the first live birth reported through vitrified-warmed oocytes in a patient with invasive ovarian cancer. Although oocyte vitrification is an alternative to be considered for fertility preservation in highly selected cases of ovarian cancer, controversial issues are discussed. Fertility preservation is a proven possibility in some cancer patients according to their age, disease and time available until the beginning of their oncological treatment. Although oocyte vitrification is an alternative to be considered for fertility preservation in highly selected cases of ovarian cancer, no live birth has been reported. We report the live birth of a healthy newborn through vitrified-warmed oocytes in a young patient with invasive mucinous ovarian carcinoma (stage Ic). Diagnosis was performed after a laparoscopic left adnexectomy. She underwent two cycles of ovarian stimulation, and 14 oocytes were vitrified before fertility-sparing surgery with uterus preservation went ahead. One year later, a transfer of two embryos was performed after the insemination of the warmed oocytes. Eighteen days after the transfer she underwent a laparotomy because of abdominal pain, vaginal bleeding and haemoperitoneum. A right cornual ectopic pregnancy in the uterus was diagnosed and a wedge resection was performed to resolve it. One week later, a viable intrauterine pregnancy was confirmed under ultrasound. An elective Caesarean section was performed at week 38 of gestation, resulting in the birth of a healthy boy weighing 2650 g. To our knowledge, this is the first live birth reported using vitrified-warmed oocytes in invasive ovarian cancer. Controversial issues are reviewed and discussed.

Cancer and fertility preservation: Barcelona consensus meeting.

Improvements in early diagnosis and treatment strategies in cancer patients have enabled younger women with cancer to survive. In addition to the stressful event of the diagnosis, patients with malignant diseases face the potential loss of the opportunity to have children. Preservation of fertility has become a challenging issue and it is still surrounded by controversies. On the basis of available evidence, a group of experts reached a consensus regarding the options for trying to preserve fertility in women with cancer: among established methods, in postpubertal women, oocyte cryopreservation is the preferred option, whereas ovarian tissue cryopreservation is the only possibility for prepubertal girls. Combining several strategies on an individual basis may improve the chances of success. Realistic information should be provided before any intervention is initiated. Counseling should offer support for patients and provide better care by understanding emotional needs, psychological predictors of distress and methods of coping. Early referral to the fertility specialist is essential as fertility preservation (FP) may improve quality of life in these patients. The information summarized here is intended to help specialists involved in the treatment of cancer and reproductive medicine to improve their understanding of procedures available for FP in young cancer patients.

Elective single-embryo transfer in oocyte donation programmes: Should it be the rule?

The aim of this study is to compare the cumulative clinical pregnancy and live birth rates (fresh embryo transfers followed by frozen-thawed embryo transfers from the same stimulated cycle) between single-embryo transfer (SET) and double-embryo transfer (DET) in an oocyte donation programme. A retrospective analysis of the outcome in 1139 recipient fresh cycles (1073 from DET and 66 from SET) with at least three available embryos for transfer was performed. The clinical pregnancy rates were similar after SET (45.5%, 30/66) and DET (57.1%, 613/1073), whereas the multiple pregnancy rate was 0% and 39.5% for SET and DET, respectively. After evaluating the results using the Kaplan-Meier survival analysis in a period of 1 year, no statistically significant differences were observed in the cumulative clinical pregnancy and live birth rates (SET 82.8% and 76.4% versus DET 77.2% and 63.7%). The results indicate that for women who have at least three available embryos in oocyte donation programmes, one single embryo should be transferred as no significant decrease in the success rate is observed and multiple pregnancy can be avoided. Clinical pregnancy rate is higher when transferring two embryos compared with one. However, this also results in a higher incidence of twin pregnancy, which is associated with increased obstetric and perinatal risks. The aim of this study was to compare the cumulative clinical pregnancy and live birth rates (fresh embryo transfers followed by frozen-thawed embryo transfers from the same stimulated cycle) between single-embryo transfer (SET) and double-embryo transfer (DET) cycles in our oocyte donation programme. A retrospective analysis of the outcome in 1139 recipient fresh cycles (1076 from DET and 66 from SET) with at least three available embryos for transfer was performed. The clinical pregnancy rates were similar after SET (45.5%, 30/66) and DET (57.1%, 613/1073), whereas the multiple pregnancy rate was 0% and 39.5% for SET and DET, respectively. The cumulative clinical pregnancy and live birth rates were similar between the two strategies (SET 82.8% versus DET 77.2%) and the same was found for the cumulative live birth rates (SET 76.4% versus DET 63.7%). Our results indicate that for women who have at least three available embryos in OD programmes, one single embryo should be transferred as no significant decrease in the success rate is observed while multiple pregnancy is avoided.

Gonadotrophin-releasing hormone-antagonists vs long agonist in in-vitro fertilization patients with polycystic ovary syndrome: a meta-analysis.

AIM: This article is a systematic review of the literature to establish whether there is an advantage in the use of GnRH antagonists (Ant) compared to the long agonist protocol (Ago) in patients with polycystic ovarian syndrome (PCOS). MATERIAL AND METHODS: The meta-analysis was conducted using the MIX software with Mantel?Haenszel weighting method and the fixed effect model. RESULTS: Five studies were identified. We analyzed 269 Ant and 303 Ago cycles. Pregnancy rates and the incidence of ovarian hyperstimulation syndrome (OHSS) were analyzed in all five studies, abortion rates were analyzed on three. Pregnancy rates did not differ between the groups: 137/269 (Ant Group) versus 172/303 (Ago Group) (OR: 0.80 CI: [0.57-1.11]). The incidence of OHSS per Ant (13/269) was significantly lower compared to the Ago (35/303) (OR: 0.47 CI: [0.24-0.92]). No difference was found between the two groups in the abortion rate: 10/77 (Ant Group) versus 9/88 (Ago Group) (OR: 1.29 CI: [0.49-3.36]). CONCLUSION: The limited evidence present in literature suggests that in patients with PCOS there is no difference between a long Ago and an Ant protocol in terms of pregnancy and abortion rates. It seems more likely that the use of the Ant may reduce the incidence of OHSS.

Prevention of prematurity by single embryo transfer.

The development of assisted reproduction techniques (ART) represents an important advance in the treatment of human infertility. However, their great effectiveness has brought with it an excessive increase in multiple pregnancy rates with the serious medical, financial and social consequences that they entail. Now, the scientific societies, the health professionals, and the infertile couples themselves are aware of these risks and have worked together to implement various strategies to deal with this situation. The result that is being obtained from the strategy of selectively reducing the number of embryos transferred is obvious. The pandemic of multiple pregnancies is being brought under control and so we have effective prevention of the obstetric and neonatal complications arising from it. It is to be hoped that it will also contribute to significantly reducing the rates of prematurity and thus of severe neonatal complications.

Endometriosis-associated infertility: surgery and IVF, a comprehensive therapeutic approach.

Infertility is a common problem presented by patients with endometriosis. At present, whichever treatment is chosen, half of patients with advanced stages of the disease will remain infertile afterwards. This observational study looked at the reproductive outcome achieved after treating a group of 825 patients aged between 20 and 40 years with endometriosis-associated infertility during the period 2001-2008. Of the 483 patients who had surgery as the primary option, 262 became pregnant (54.2%). Among the patients who did not become pregnant, 144 underwent 184 IVF cycles and 56 additional pregnancies were obtained (30.4% clinical pregnancy rate per retrieval). It is notable that, before any treatment, patients with endometriosis had a poorer ovarian reserve than the control group. The combined strategy of endoscopic surgery and subsequent IVF led to a total of 318 pregnancies, which represents a combined clinical pregnancy rate of 65.8%. This percentage is significantly higher than that obtained with surgery alone (P < 0.0001), with 173 patients who were not operated on and who went to IVF as the primary option (P < 0.0001) and with 169 patients who had no treatment and achieved 20 spontaneous pregnancies (P < 0.0001).

Pronuclear morphology, embryo development and chromosome constitution.

The aim of the present study was to evaluate the usefulness of pronuclear patterns, according to the classifications of Tesarik and Scott, as predictors of embryo chromosome constitution. Up to 73 preimplantation genetic diagnosis/preimplantation genetic screening (PGD/PGS) cycles were analysed in this retrospective study including 17 cycles of translocation carriers and 56 PGS cycles. A total of 331 biopsied embryos were studied assessing pronuclear (PN) pattern, embryo quality and chromosome constitution. As regards to the relationship between PN pattern and embryo quality, the data obtained in this study show no correlation between both parameters. Although there were no significant differences when comparing the distribution of chromosomally normal and abnormal embryos with respect to embryo quality, such differences were observed when distinguishing between normal, aneuploid and polyploid embryos. The results show that the PN pattern using Tesarik's and Scott's classification systems is not related to the embryo developmental potential or its chromosome constitution. Therefore, in the context of a PGD/PGS programme, the PN pattern cannot be used as a tool to predict embryo quality or chromosome status.

Mild stimulation in assisted reproduction.

The conventional ovarian stimulation protocols currently applied have several drawbacks arising from the intense ovarian stimulation and from the high financial cost. Recently, new concepts such as mild stimulation and friendly in vitro fertilisation have rapidly acquired great popularity among infertile patients although the medical world is still reluctant to apply these protocols generally. We have observed that although with soft stimulation fewer oocytes are retrieved, pregnancy rates are not affected if more than five oocytes are obtained in the follicular aspiration. Another important issue is the additional value of the embryo cryopreservation programmes that will result in cumulative pregnancy rates no different from those obtained with conventional protocols. The benefits of combining these mild stimulation protocols with a selective reduction of the number of embryos to replace have helped us in reducing the incidence of multiple pregnancies and the global cost of the treatment.

Poor prognosis for ovarian response to stimulation: results of a randomised trial comparing the flare-up GnRH agonist protocol vs. the antagonist protocol.

OBJECTIVE: To determine the efficacy of the flare-up agonist and the antagonist protocols in patients with poor prognosis for ovarian response. METHODS: A randomised trial was conducted on two hundred and twenty-one women considered as having poor prognosis for ovarian response to stimulation, based on previous cycles or clinical criteria. All women were prospectively randomised into two groups of treatment (flare-up group and antagonist group) by computer-assisted randomisation in a 1:1 ratio. The main outcome measure was clinical pregnancy rate. RESULTS: Groups were homogeneous in age and baseline characteristics. Duration of stimulation, gonadotropin consumption, number of oocytes retrieved and number and quality of embryos transferred did not differ significantly between the groups. E(2) level the day of hCG administration was significantly higher in the flare-up group. Pregnancy rates per started cycle were 15% in the flare-up group and 14.1% in the antagonist group. Cancellation rates were 12.5% in the flare-up group and 16.3% in the antagonist group. None of these differences reached statistical significance. CONCLUSIONS: No statistically significant differences were observed between the two protocols regarding clinical pregnancy rates. In patients with poor prognosis for ovarian response, the flare-up agonist and the antagonist protocols were comparable regarding clinical pregnancy rates.

Beliefs, attitudes and funding of assisted reproductive technology: Public perception of over 6,000 respondents from 6 European countries.

BACKGROUND: Fertility rates in Europe are among the lowest in the world, which may be attributed to both biological and lifestyle factors. Cost and reimbursement of fertility treatments vary across Europe, although its citizens enjoy wide access to fertility care. Since few regional studies evaluating public support for fertility treatment exist, we conducted the Listening IVF and Fertility in Europe (LIFE) survey to ascertain public perception of in vitro fertilization (IVF) and gamete donation as a treatment for infertility among European men and women. METHODS AND FINDINGS: This survey was distributed via an online questionnaire to 8,682 individuals who were voluntary participants in an online research panel residing in France, Germany, Italy, Spain, Sweden, or the UK. The survey covered items to determine respondents' beliefs regarding IVF and its success, the need for public funding, the use of IVF among modern families with different lifestyles, and the support for gamete donation. Results were analyzed by age, country of origin, sex, and sexual orientation. A total of 6,110 (70% of total) men and women responded. Among all respondents, 10% had undergone IVF treatment and 48% had considered or would consider IVF in case of infertility. Respondents estimated IVF mean success rate to be 47% and over half of respondents believed that availability of IVF would encourage people to delay conception. Although 93% of respondents believed that IVF treatment should be publicly funded to some extent, a majority believed that secondary infertility or use of fertility treatments allowing to delay parenthood should be financed privately. Survey respondents believed that the mean number of stimulated IVF cycles funded publicly should be limited 2 to 3 (average 2.4). 79% of respondents were willing to pay for IVF if needed with a mean amount of 5,400 € for a child brought to life through IVF. According to respondents, mean minimum and maximum ages for IVF should be 29 and 42 years old, respectively. The current survey showed support for egg and sperm donation (78%), for IVF in single women (61%) and for same-sex female couples (64%). When analyzing the results per group (i.e., sex, age, sexual orientation, and countries), youngest age groups, homosexuals, bisexuals, German respondents, and men had similar overall positive attitudes and beliefs toward IVF and opinions on public funding. Perceived limits to availability were stronger in women. CONCLUSION: Overall, the survey results demonstrate a positive attitude among respondents in an online panel toward IVF, gamete donation, and support for public funding for fertility treatment. These findings could potentially drive discussions between patients and prescribers to explore IVF treatment and among legislators and payers to support public funding for these procedures.

Clinical success of IUI cycles with donor sperm is not affected by total inseminated volume: a RCT.

STUDY QUESTION: What is the impact on live birth rates (LBR) when a donor IUI (dIUI) cycle is performed with an insemination volume of 0.5 mL versus the usual 0.2 mL? SUMMARY ANSWER: LBR after a dIUI cycle is no different when performed with 0.5 versus 0.2 mL. WHAT IS ALREADY KNOWN: An IUI has an important role in the treatment of severe male infertility, and is often used in same-sex female couples and single parents. Different variables have been studied to determine factors correlated with clinical outcomes (IUI scheduling, ovarian stimulation, sperm parameters) but little is known about the inseminated volume. The use of conical bottom test tubes could contribute substantially to the loss of inseminated spermatozoa because it precludes the total recovery of the sample. Additionally, the insemination catheter could uphold this reduction causing sperm adhesion on the inner walls of the insemination catheter, decreasing even more the total inseminated volume. It is expected that utilizing an IUI approach that increases sperm volume in the fallopian tubes (0.5 mL rather than 0.2 mL) at the time of ovulation will lead to higher LBRs. To avoid bias related to sperm quality, the study population was restricted to dIUI cycles. STUDY DESIGN SIZE AND DURATION: A parallel-group, double-blinded, RCT, including patients undergoing natural or stimulated dIUI, was performed between March 2013 and April 2015. dIUI cycles (n = 293) were randomized through a computer-generated list to undergo insemination with 0.2 mL (control group) or 0.5 mL (study group), of which 24 were excluded (protocol deviation) and 269 received the allocated intervention. Patients with the presence of tubal factor infertility, grades III-IV endometriosis, >3 previous dIUI cycles or with ≥3 follicles >14 mm were excluded. The study was designed with 80% power to detect a 5% difference in LBR with a reference of 15% and a two-tailed 5% significance level. The required sample size was 118 per group. PARTICIPANTS/MATERIALS SETTING AND METHOD: There were 143 cycles (0.2 mL group) and 126 cycles (0.5 mL group). The primary end-point of the trial was LBR per dIUI cycle in both treatment groups. Clinical pregnancy rate and miscarriage rate were evaluated as secondary outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: No adverse events were reported during the study trial. Study groups (0.2 versus 0.5 mL, respectively) were similar in age (35.8 ± 3.9 versus 35.4 ± 4.0 years: mean±SD), and had similar anti-Mullerian hormone levels (2.2 ± 1.8 versus 2.0 ± 1.5 ng/mL), basal antral follicle count (13.2 ± 6.4 versus 13.6 ± 6.0), BMI (23.5 ± 3.9 versus 23.7 ± 4.1 kg/m2), number of follicles >17 mm (1.1 ± 0.5 versus 1.1 ± 0.5), total gonadotrophin dose (553.1 ± 366.3 versus 494.6 ± 237.1 IU), and total motile sperm count (8.22 ± 7.1 versus 7.7 ± 5.7 million). Similar clinical pregnancy rates (18.9% (27/143) versus 19.8% (25/126), NS), LBRs (15.4% (22/143) versus 19.0% (24/126), NS) and miscarriage rates (18.5% (5/27) versus 4.0% (1/25), NS) were observed between groups. LIMITATIONS REASONS FOR CAUTION: The study was not powered to detect differences in the secondary outcomes, clinical pregnancy and miscarriage rates. The randomization was performed at the dIUI cycle level, therefore, the results are reported as success rate per dIUI cycle rather than per patient. WIDER IMPLICATIONS OF THE FINDINGS: This is the first RCT to show that the inseminated volume is not correlated with the probability of a live birth. The miscarriage rate was higher in the 0.2 mL group, although this difference was not statistically significant. If the lower miscarriage rate observed in the 0.5 mL group is confirmed, this could be related to the presence of uterine contractions similar of those generated during sexual intercourse, which may be implicated in the inception of early biochemical embryo-endometrium communication. STUDY FUNDING/COMPETING INTERESTS: All authors declare having no conflict of interest with regard to this trial. No funding was received for this study. This research was performed under the auspices of 'Càtedra d'Investigació en Obstetrícia I Ginecologia' of the Department of Obstetrics, Gynaecology and Reproductive Medicine, Hospital Universitari Quiron-Dexeus, Universitat Autònoma de Barcelona. TRIAL REGISTRATION NUMBER: The trial was registered at clinicaltrials.gov (Identifier: NCT03006523).