Impact of dehydroepiandrosterone sulfate and free androgen index on pregnancy and neonatal outcomes in PCOS patients.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with infertility and pregnancy complications. The pathogenesis of PCOS and its impact on reproductive function may be influenced by the source of androgens, including testosterone, free androgen, dehydroepiandrosterone sulfate (DHEAS). However, the differential effects of these androgen on pregnancy and neonatal outcomes and the cut-off value of East Asian population with PCOS remain unclear. METHODS: A retrospective cohort study was conducted at the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University from January 2015 to November 2022, involving 636 cycles of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Subgroup analyses were performed using cut-off values of 6.4 for free androgen index (FAI), 9.5 µmol/L for DHEAS. Pregnancy and neonatal outcomes were compared between groups. Restricted cubic spline (RCS) was used to identify significant cut-off values affecting pregnancy. RESULTS: Higher FAI levels (> 6.4) were associated with decrease in clinical pregnancy rate (PR) (50.61% vs. 41.66%, p = 0.024), live birth rate (LBR) (42.42% vs. 32.35%, p = 0.011). When DHEAS levels exceeded 9.5 µmol/L, there was a significant decrease in clinical PR (51.27% vs. 42.73%, P = 0.039), LBR (42.73% vs. 32.73%, P = 0.012). Negative correlations were also observed between DHEAS levels and cumulative pregnancy rate (70.57% vs 56.62% p = 0.002) and cumulative live birth rate (CLBR) (59.35% vs 43.37%, p = 0.0007). Both FAI and DHEAS elevated is associated with the lowest clinical pregnancy rate (37.84%). Conversely, when solely FAI is elevated, the pregnancy rate increases to 52.38%, while an elevation in DHEAS alone is associated with a pregnancy rate of, both of which are lower than when neither FAI nor DHEAS are elevated (60.68%). The live birth rates exhibit a similar trend (30.00% vs 40.00% vs 41.83% vs 44.48%). RCS revealed a significant decrease in CPR and CLBR when DHEA levels exceeded 7.69 umol/L, while the cut-off value of FAI was 6.36 for CPR and CLBR. CONCLUSION: In conclusion, PCOS patients with biochemical hyperandrogenism show unsatisfactory clinical PR and CLBR when undergoing assisted reproductive technology (ART). This may be attributed to the influence of both adrenal-derived DHEAS and ovarian-derived FAI on the unfavorable pregnancy outcomes.

Coexistence of Endometriosis and Thyroid Autoimmunity in Infertile Women: Impact on in vitro Fertilization and Reproductive Outcomes.

OBJECTIVES: The objective of the study was to evaluate the prevalence and impact of impaired thyroid-stimulating hormone (TSH) levels on the reproductive outcomes of in vitro fertilization patients diagnosed with endometriosis and compared to controls without endometriosis. DESIGN: This is a retrospective cohort study on prospectively collected data. SETTING: The study was conducted at tertiary care university hospital. PARTICIPANTS: Participants were infertile women with histopathological diagnosis of endometriosis. METHODS: For 12 months (January 2018 to January 2019), women were deemed suitable and subsequently divided according to serum TSH levels above or below 2.5 mIU/L and compared to patients without endometriosis. Needed sample size was at least 41 patients for each cohort of women. Co-primary outcomes were the live birth rate (LBR), clinical pregnancy rate (CPR), and pregnancy loss rate (PLR). RESULTS: Overall, 226 women (45 with endometriosis and 181 controls without endometriosis) were included. Diagnoses of Hashimoto thyroiditis were significantly more frequent in women with rather than without endometriosis (14/45 [31.1%] vs. 27/181 [14.9%]; p = 0.012). Similarly, in women with endometriosis, Hashimoto diagnosis rates were higher with TSH ≥2.5 mIU/L compared to TSH <2.5 mIU/L (9/15 [60%] vs.5/30 [16.6%]; p = 0.001) so were the Hashimoto diagnosis rates in control group (women without endometriosis) with TSH ≥2.5 mIU/L compared to TSH <2.5 mIU/L (17/48 [35.4%] vs. 10/133 [7.5%], respectively; p = 0.001). Effect size analysis confirmed an increased risk of Hashimoto thyroiditis in women with endometriosis and TSH ≥2.5 mIU/L compared to women with endometriosis and TSH <2.5 mIU/L (risk ratio [RR] 3.60 [95% CI 1.46-8.86]) and in women with endometriosis and TSH ≥2.5 mIU/L compared to non-endometriotic euthyroid patients (RR 7.98 [95% CI 3.86-16.48]). Dysmenorrhea risk was higher in endometriotic euthyroid women compared to euthyroid patients with no endometriosis (RR 1.87 [95% CI 1.21-2.87]). The risk was still increased in euthyroid women with endometriosis relative to dysthyroid women with no endometriosis (RR 1.97 [95% CI 1.11-3.50]). There were no significant differences between the four groups for CPR, LBR, PLR and retrieved oocytes, immature oocytes, degenerated and unfertilized oocytes, cultured blastocysts, embryos and transferred embryos. LIMITATIONS: Limitations of the study were retrospective design, limited sample size, and use of different ovarian stimulation protocol. CONCLUSIONS: Thyroid autoimmunity seems more common in women with endometriosis and TSH over 2.5 mIU/L. However, there was no significant impact on in vitro fertilization and reproductive outcomes related to the coexistence of endometriosis, Hashimoto disease, and higher TSH levels. Due to limitations of the study, additional evidence is required to validate the abovementioned findings.

Intrauterine administration of paternal and maternal peripheral blood mononuclear cells mix as solution for repeated implantation failure.

To date, implantation is the rate-limiting step for the success of in vitro fertilization (IVF) treatment. Accumulating evidence suggests that immune cells contribute to embryo implantation, and several therapeutic approaches have been proposed for the treatment of recurrent implantation failure (RIF). Endometrial immune modulation with autologous activated peripheral blood mononuclear cells (PBMCs) is one of the most widely used protocols. However, the effect of intrauterine insemination of mixed paternal and maternal-activated PBMCs has not yet been attempted and studied. The aim of our study is to test the effect of the addition of paternal lymphocytes on the implantation rate in RIF patients. Mononuclear cells were isolated from the peripheral blood of 98 RIF patients and cultured for 72 h before insemination into the endometrial cavity 48 h before embryo transfer. Our patients were divided into 4 groups according to the type and number of PBMCs inseminations. Our study shows that activated PBMCs promoted clinical pregnancy rates (CPR) in all groups. Moreover, we found that the groups injected with more than 2 million cells showed a better clinical outcome and, more interestingly, patients inseminated with both paternal and maternal activated PBMCs showed the highest CPR, reaching 47.2%, in addition to the highest implantation rate 31. 2% and the live birth rate 41.39%. Our work demonstrates the importance of administering a large number of activated PBMCs with the addition of paternal activated PBMCs to immunomodulate the endometrium for the success of in vitro fertilization in RIF patients.

Evaluating Pregnancy Rates in Fertility Awareness-Based Methods for Family Planning: Simulated Comparison of Correct Use to Avoid, Method-Related, and Total Pregnancy Rates.

Fertility awareness-based methods (FABMs), also known as natural family planning (NFP), enable couples to identify the days of the menstrual cycle when intercourse may result in pregnancy ("fertile days"), and to avoid intercourse on fertile days if they wish to avoid pregnancy. Thus, these methods are fully dependent on user behavior for effectiveness to avoid pregnancy. For couples and clinicians considering the use of an FABM, one important metric to consider is the highest expected effectiveness (lowest possible pregnancy rate) during the correct use of the method to avoid pregnancy. To assess this, most studies of FABMs have reported a method-related pregnancy rate (a cumulative proportion), which is calculated based on all cycles (or months) in the study. In contrast, the correct use to avoid pregnancy rate (also a cumulative proportion) has the denominator of cycles with the correct use of the FABM to avoid pregnancy. The relationship between these measures has not been evaluated quantitatively. We conducted a series of simulations demonstrating that the method-related pregnancy rate is artificially decreased in direct proportion to the proportion of cycles with intermediate use (any use other than correct use to avoid or targeted use to conceive), which also increases the total pregnancy rate. Thus, as the total pregnancy rate rises (related to intermediate use), the method-related pregnancy rate falls artificially while the correct use pregnancy rate remains constant. For practical application, we propose the core elements needed to assess correct use cycles in FABM studies. Summary: Fertility awareness-based methods (FABMs) can be used by couples to avoid pregnancy, by avoiding intercourse on fertile days. Users want to know what the highest effectiveness (lowest pregnancy rate) would be if they use an FABM correctly and consistently to avoid pregnancy. In this simulation study, we compare two different measures: (1) the method-related pregnancy rate; and (2) the correct use pregnancy rate. We show that the method-related pregnancy rate is biased too low if some users in the study are not using the method consistently to avoid pregnancy, while the correct use pregnancy rate obtains an accurate estimate. Short Summary: In FABM studies, the method-related pregnancy rate is biased too low, but the correct use pregnancy rate is unbiased.

A surplus no more? Variation in krill availability impacts reproductive rates of Antarctic baleen whales.

The krill surplus hypothesis of unlimited prey resources available for Antarctic predators due to commercial whaling in the 20th century has remained largely untested since the 1970s. Rapid warming of the Western Antarctic Peninsula (WAP) over the past 50 years has resulted in decreased seasonal ice cover and a reduction of krill. The latter is being exacerbated by a commercial krill fishery in the region. Despite this, humpback whale populations have increased but may be at a threshold for growth based on these human-induced changes. Understanding how climate-mediated variation in prey availability influences humpback whale population dynamics is critical for focused management and conservation actions. Using an 8-year dataset (2013-2020), we show that inter-annual humpback whale pregnancy rates, as determined from skin-blubber biopsy samples (n = 616), are positively correlated with krill availability and fluctuations in ice cover in the previous year. Pregnancy rates showed significant inter-annual variability, between 29% and 86%. Our results indicate that krill availability is in fact limiting and affecting reproductive rates, in contrast to the krill surplus hypothesis. This suggests that this population of humpback whales may be at a threshold for population growth due to prey limitations. As a result, continued warming and increased fishing along the WAP, which continue to reduce krill stocks, will likely impact this humpback whale population and other krill predators in the region. Humpback whales are sentinel species of ecosystem health, and changes in pregnancy rates can provide quantifiable signals of the impact of environmental change at the population level. Our findings must be considered paramount in developing new and more restrictive conservation and management plans for the Antarctic marine ecosystem and minimizing the negative impacts of human activities in the region.

Efficacy of Hysteroscopy in Improving Fertility Outcomes in Women Undergoing Assisted Reproductive Technique: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Usefulness of hysteroscopy before assisted reproductive technique (ART) was considered debatable. However, over the last decade, several new trials have been added to available literature. We aimed to assess the impact of diagnostic and operative hysteroscopy on reproductive outcomes of infertile women with and without intrauterine abnormalities. MATERIALS AND METHODS: MEDLINE, Scopus, SciELO, Embase, Cochrane Library at CENTRAL, PROSPERO, CINAHL, grey literature, conference proceedings, and international controlled trials registries were searched without temporal, geographical, or language restrictions. Randomized controlled trials (RCTs) of infertile women comparing hysteroscopy versus no hysteroscopy prior to the first ART or after at least one failed attempt were included. RCTs of infertile women with intrauterine pathology comparing diagnostic versus operative hysteroscopy were included in separate analysis. Random-effect meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Grading of Recommendations, Assessment, Development and Evaluation and Cochrane criteria were used for quality of evidence and risk of bias assessment. Primary outcome was live birth rate (LBR). Secondary outcomes were clinical pregnancy (CPR) and pregnancy loss rate. RESULTS: Fifteen studies (5,038 women) were included. Compared to no hysteroscopy before first or after failed ART attempts, moderate-quality evidence showed that hysteroscopy increased the LBR (relative risk [RR] 1.24, 95% confidence interval [CI] 1.09-1.43, I2 = 21%), confirmed by subgroup analysis for women with failure after one or more ART cycles (RR 1.43, 95% CI: 1.19-1.72, I2 = 0%) but not before the first ART. Moderate-quality evidence showed that it increased the CPR (RR 1.36, 95% CI: 1.18-1.57; I2 = 51%), confirmed in subgroup analysis for both implantation failure (RR 1.40, 95% CI: 1.12-1.74, I2 = 52%) and before first ART (RR 1.32, 95% CI: 1.11-1.57, I2 = 42%). Low-quality data suggest that operative hysteroscopy increases CPR when used to treat intrauterine pathologies (RR 2.13, 95% CI: 1.56-2.92, I2 = 0%). CONCLUSIONS: Although moderate-quality evidence supports performing hysteroscopy before ART in women with history of implantation failure, hysteroscopic evaluation of uterine cavity should be considered a first-line technique in all infertile women undergoing ART. Additional high-quality RCTs are still needed, particularly to assess yield during couple's initial evaluation even before ART is considered.

Luteal function in cyclic goats treated with human chorionic gonadotropin administered by intramuscular or intravaginal routes at the time of artificial insemination.

Human chorionic gonadotropin (hCG) has been used to improve goats reproductive efficiency. This study aimed to (i) evaluate if hCG administered by the intramuscular (i.m.) or intravaginal (i.vag.) route can be detected by a rapid ß-hCG test in blood plasma samples and (ii) document ovarian effects of hCG administered by both routes at the time of artificial insemination (AI) performed 60 h after oestrus synchronization in goats. Twenty-two Alpine goats received two i.m. injections of 30 µg of d-cloprostenol (Prolise®, Tecnopec, São Paulo, Brazil) 7.5 days apart. One day after the onset of oestrus (at the time of AI), the goats were randomly allocated to one of the three groups that received: control (n = 7): 0.3 ml of saline solution intravaginally; hCGi.m. (n = 7): 300 IU of hCG (Vetecor®; Hertape-Calier, São Paulo, Brazil) i.m. and hCGi.vag. (n = 8): 300 IU of hCG deposited intravaginally. Blood samples were drawn at -1, 3, 6, 9 and 24 h after as well as on days 3, 7, 10, 13, 17 and 21 after hCG treatment/AI. All animals tested negative for hCG (ECO Diagnóstica, Corinto, Brazil) at -1 h, and all control animals tested negative throughout the entire blood collection period. All hCGi.m. animals tested positive from 3 h until D3 post-AI but only 50% of hCGi.vag. goats tested positive during the present study. In all animals studied, mean circulating P4 concentrations increased (p < .05) from D3 to D7 after AI and then declined (p < .05) from D10 to D17 in control and hCGi.m. groups and from D17 to D21 in the hCGi.vag. group. Total cross-sectional luteal area (CLA), mean colour Doppler area (DA), DA/CLA, mean high-velocity Doppler area and HVDA/CLA all declined (p < .05) by D17-D21 in all animals studied. In summary: (i) human chorionic gonadotropin could consistently be detected in blood samples using the rapid ß-hCG test only in the hCGi.m. group; and (ii) there were no significant differences in the mean pregnancy rate, circulating P4 concentrations and various luteal parameters studied among Control, hCGi.m. and hCGi.vag. dose.

Influence of weaning management at 30, 75 and 180 days of age on non-esterified fatty acids and reproductive performance in beef cows.

This study aimed to investigate the effect of age at weaning of calves on non-esterified fatty acids (NEFA) and reproductive parameters of beef cows. Animals (n = 65) were randomly assigned to three treatments after calving: hyper-early weaning (W30) at 32 ± 0.89 days, early weaning (W75) at 77 ± 0.95 days, and conventional weaning (W180) at 183 ± 0.82 days. Body weight (BW) and body condition score (BCS) were evaluated at parturition (AP) and at 30, 45, 64, 81, 100 and 115 days postpartum (dPP). Blood samples were collected to analyze NEFA levels and progesterone (P4) at 30, 45, 64 and 81 dPP. Higher BW and BCS were observed from 64 to 115 dPP in W30 cows than W180 ones (p < 0.05). Cows subjected to W30 condition had higher levels of NEFA at 30 dPP compared to 64 and 81 dPP (p < 0.05). We also observed that cows from W180 group showed decreased levels of NEFA at 30 dPP compared to 45 (p < 0.01) and 64 dPP (p < 0.05). The highest P4 level was observed at 64 dPP in W30 cows compared to W75 and W180 (p < 0.05). We also observed higher CR of W30 (86%) compared to W180 (47%) at 45 dPP (p < 0.05). The overall pregnancy rate (PR) was higher for W30 (95.5%) than W180 (73.9%). In addition, higher BW at calving and P4 levels at 30 dPP were positively correlated with the possibility of pregnancy (p < 0.05). Improvement in BW and BCS were observed in cows subjected to hyper-early weaning management. However, levels of NEFA decreased as the postpartum period progressed. We concluded that cows who weaned calves hyper-early have greater chances of increasing cyclicity and PRs.

The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows.

AIM: OvSynch is a hormonal protocol for synchronization of estrus and use of artificial insemination (AI) at an optimal time without adverse effects on the ovaries or uterus. This study investigated the use of noninvasive color Doppler ultrasound to assess changes in uterine and vaginal blood flow during the Ovsynch program for synchronization of estrus and its relation to the pregnancy rates in Holstein cows. MATERIALS AND METHODS: The experimental cows received an intramuscular dose of 10 µg of a GnRH analogue (G1), followed 7 days later with an intramuscular injection of synthetic prostaglandin F2α (P: PGF2α) analogue (500 µg cloprostenol sodium), and given a 10 µg, injection of the GnRH analogue (G2) i.m. 48 h after the PGF2α treatment, and the cows were bred 14-16 h after. Uterine and vaginal perfusion were investigated by performing transrectal Doppler ultrasonography of both the uterine and vaginal arteries in Holstein cows at different time points during the Ovsynch program to determine: peak systolic velocity (PSV), time-averaged maximum velocity (TAMV), the volume of blood flow (BFV), pulsatility index (PI), resistance index (RI), resistance impedance (S/D) and diameters of uterine (UA) and vaginal (VA) arteries. Steroid hormones were also assayed. Transrectal ultrasonography (TUS) was performed at 32 and 60 days to confirm the pregnancy per artificial insemination (P/AI). RESULTS: The uterine PSV, TAMV, and PV were greater at the time of the cloprostenol sodium and second GnRH injections (p<0.05) than at the time of the first GnRH injection. The vaginal PSV, PV were greater at the time of the cloprostenol sodium than at the time of the first and second GnRH injections (p<0.05). The receiver operating characteristic curve (ROC curve) indicated a high correlation between the uterine and vaginal blood flow and the rate of the pregnancy (p<0.05). The area under the ROC curve was 0.920 and 0.87 (p<0.05) for vaginal and uterine arteries respectively at time of G2. The serum levels of progesterone, estrogen and cortisol were correlated with the P/AI (p<0.05). The P/AI significantly decreased from 43.9 % at 32 d to 35.37 % at 60 d. CONCLUSION: These results indicate that noninvasive Doppler ultrasonography is a valid method to evaluate changes in the characteristics of uterine and vaginal blood flow in cows during the Ovsynch protocol. Furthermore, vaginal and uterine blood flow are two determinant factors for the higher conception rates in Holstein dairy cows.

Recipients' pregnancy rate was affected by season but not by the temperature-humidity index (THI) in an equine commercial ET programme in Southern Europe.

This study retrospectively analysed the effects of different environmental factors such as the photoperiod, temperature/humidity index of 19 years of a commercial embryo transfer programme performed in central Italy. From 340 donors of different breeds and aged between 2 and 25 years, 576 embryos of an excellent or good quality were obtained by uterine flushing on days 7-8 after ovulation. The embryos were transferred to 259 recipients, aged between 2 and 16 years, and belonging to different breeds. Both the donors and the recipients were employed for several cycles/years. At the time of transfer, the recipients were in diestrus, from day 4 to day 8 after ovulation, and were classified as excellent or good based on clinical examination findings. Out of the total number of embryos transferred, 437 pregnancies were obtained at 14 days (75.9%), with 48/437 (10.1%) embryonic losses at 40 days; with no significant differences among years. Significant differences (p < .05) were observed between 14-day pregnancy rates for transfers performed during the spring transition and breeding seasons (77.1%) compared to those performed during the autumn transitional season (57.9%). No effect of temperature/humidity index was found on pregnancy rates or pregnancy losses after the transfer to the recipients (p > .05). Embryo transfer during autumn was less successful than the transfers performed during the spring transition and the breeding season.

Effect of endometrial thickness changes on clinical pregnancy rates after progesterone administration in a single frozen-thawed euploid blastocyst transfer cycle using natural cycles with luteal support for PGT-SR- and PGT-M-assisted reproduction: a retrospective cohort study.

BACKGROUND: To investigate whether the endometrial thickness change ratio from the progesterone administration day to the blastocyst transfer day is associated with pregnancy outcomes in a single frozen-thawed euploid blastocyst transfer cycle. METHODS: All patients used natural cycles with luteal support for endometrial preparation and selected a single euploid blastocyst for transfer after a biopsy for preimplantation genetic testing. The endometrial thickness was measured by transvaginal ultrasound on the progesterone administration day and the transfer day, the change in endometrial thickness was measured, and the endometrial thickness change ratio was calculated. According to the change rate of endometrial thickness, the patients were divided into three groups: the endometrial thickness compaction group, endometrial thickness non-change group and endometrial thickness expansion group. Among them, the endometrial thickness non-change and expansion groups were combined into the endometrial thickness noncompaction group. RESULTS: Ultrasound images of the endometrium in 219 frozen-thawed euploid blastocyst transfer cycles were evaluated. The clinical pregnancy rate increased with the increase in endometrial thickness change ratio, while the miscarriage rate and live birth rate were comparable among the groups. The multiple logistic regression results showed that in the fully adjusted model a higher endometrial thickness change ratio (per 10%) was associated with a higher clinical pregnancy rate (adjusted odds ratio [aOR] 1.29; 95% confidence interval [CI], 1.01-1.64; P = .040). Similarly, when the patients were divided into three groups according to the change rate of endometrial thickness, the endometrial thickness noncompaction group had a significant positive effect on the clinical pregnancy rate compared with the endometrial thickness compaction group after adjusting for all covariates. CONCLUSIONS: In frozen-thawed euploid blastocyst transfer cycles in which the endometrium was prepared by natural cycles with luteal support, the clinical pregnancy rate was higher in cycles without endometrial compaction after progesterone administration.

Meta-analysis of the embryo freezing transfer interval.

BACKGROUND: The decision of whether frozen embryo transfer (FET) should be performed in the cycle immediately after OPU or at least one cycle later is controversial. FET could improve pregnancy rates in IVF; however, how much time is needed for the endometrium to return to optimal receptivity after ovarian stimulation is not known. METHODS: Electronic search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify studies providing data on the influence of the interval between embryo freezing (or OPU) and FET in FET cycles published between January 1, 2007, and February 1, 2020. MAIN FINDINGS: Data analyzed indicated that in the immediate FET cycles, there was a trend to an increased biochemical pregnancy rate (RR = 1.08; CI = 1.00-1.18), whereas the clinical pregnancy rate was somewhat higher, but without reaching statistical significance (RR = 1.07; CI = 0.99-1.15). The live birth rate was similar in the two groups (RR = 1.05; CI = 0.95-1.15), as was the implantation rate (RR = 0.98; CI = 0.83-1.16). Stratifying by embryo stage or FET type (freeze-all or FET after failed fresh transfer) showed no differences. CONCLUSION: Systematically delaying FET does not offer benefits to IVF outcomes. In addition, immediate transfer is associated with a nonsignificant trend to better clinical pregnancy rate and it also avoids the psychological effects of prolonging the stress on prospective parents.

Cumulative live birth rates for women returning to ART treatment for a second ART-conceived child.

STUDY QUESTION: What are the success rates for women returning to ART treatment in the hope of having a second ART-conceived child. SUMMARY ANSWER: The cumulative live birth rate (LBR) for women returning to ART treatment was between 50.5% and 88.1% after six cycles depending on whether women commenced with a previously frozen embryo or a new ovarian stimulation cycle and the assumptions made regarding the success rates for women who dropped-out of treatment. WHAT IS KNOWN ALREADY: Previous studies have reported the cumulative LBR for the first ART-conceived child to inform patients about their chances of success. However, most couples plan to have more than one child to complete their family and, for that reason, patients commonly return to ART treatment after the birth of their first ART-conceived child. To our knowledge, there are no published data to facilitate patient counseling and clinical decision-making regarding the success rates for these patients. STUDY DESIGN, SIZE, DURATION: A population-based cohort study with 35 290 women who commenced autologous (using their own oocytes) ART treatment between January 2009 and December 2013 and achieved their first treatment-dependent live birth from treatment performed during this period. These women were then followed up for a further 2 years of treatment to December 2015, providing a minimum of 2 years and a maximum of 7 years of treatment follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cycle-specific LBR and cumulative LBR were calculated for up to six complete ART cycles (one ovarian stimulation and all associated transfers). Three cumulative LBR were calculated based on the likelihood of success in women who dropped-out of treatment (conservative, optimal and inverse probability-weighted (IPW)). A multivariable logistic regression model was used to predict the chance of returning to ART treatment for a second ART-conceived child, and a discrete time logistic regression model was used to predict the chance of achieving a second ART-conceived child up to a maximum of six complete cycles. The models were adjusted for patient characteristics and previous and current treatment characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Among the women who had their first ART-conceived live birth, 15 325 (43%) returned to treatment by December 2015. LBRs were consistently better in women who recommenced treatment with a previously frozen embryo, compared to women who underwent a new ovarian stimulation cycle. After six complete cycles, plus any surplus frozen embryos, the cumulative LBR was between 60.9% (95% CI: 60.0-61.8%) (conservative) and 88.1% (95% CI: 86.7-89.5%) (optimal) [IPW 87.2% (95% CI: 86.2-88.2%)] for women who recommenced treatment with a frozen embryo, compared to between 50.5% (95% CI: 49.0-52.0%) and 69.8% (95% CI: 67.5-72.2%) [IPW 68.1% (95% CI: 67.3-68.9%)] for those who underwent a new ovarian stimulation cycle. The adjusted odds of a second ART-conceived live birth decreased for women ≥35 years, who waited at least 3 years before returning to treatment, or who required a higher number of ovarian stimulation cycles or double embryo transfer to achieve their first child. LIMITATIONS, REASONS FOR CAUTION: Our estimates do not fully account for a number of individual prognostic factors, including duration of infertility, BMI and ovarian reserve. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to report success rates for women returning to ART treatment to have second ART-conceived child. These age-specific success rates can facilitate individualized counseling for the large number of patients hoping to have a second child using ART treatment. STUDY FUNDING/COMPETING INTEREST(S): No funding was received to undertake this study. R. Paul and O. Fitzgerald have nothing to declare. D. Lieberman reports being a fertility specialist and receiving non-financial support from MSD and Merck outside the submitted work. C. Venetis reports being a fertility specialist and receiving personal fees and non-financial support from MSD, personal fees and non-financial support from Merck Serono and Beisins and non-financial support from Ferring outside the submitted work. G.M. Chambers reports being a paid employee of the University of New South Wales, Sydney (UNSW) and Director of the National Perinatal Epidemiology and Statistics Unit (NPESU), UNSW. The Fertility Society of Australia (FSA) contracts UNSW to prepare the Australian and New Zealand Assisted Reproductive Technology Database (ANZARD) annual report series and benchmarking reports. TRIAL REGISTRATION NUMBER: NA.

Declining reproductive success in the Gulf of St. Lawrence's humpback whales (Megaptera novaeangliae) reflects ecosystem shifts on their feeding grounds.

Climate change has resulted in physical and biological changes in the world's oceans. How the effects of these changes are buffered by top predator populations, and therefore how much plasticity lies at the highest trophic levels, are largely unknown. Here endocrine profiling, longitudinal observations of known individuals over 15 years between 2004 and 2018, and environmental data are combined to examine how the reproductive success of a top marine predator is being affected by ecosystem change. The Gulf of St. Lawrence, Canada, is a major summer feeding ground for humpback whales (Megaptera novaeangliae) in the North Atlantic. Blubber biopsy samples (n = 185) of female humpback whales were used to investigate variation in pregnancy rates through the quantification of progesterone. Annual pregnancy rates showed considerable variability, with no overall change detected over the study. However, a total of 457 photo-identified adult female sightings records with/without calves were collated, and showed that annual calving rates declined significantly. The probability of observing cow-calf pairs was related to favourable environmental conditions in the previous year; measured by herring spawning stock biomass, Calanus spp. abundance, overall copepod abundance and phytoplankton bloom magnitude. Approximately 39% of identified pregnancies were unsuccessful over the 15 years, and the average annual pregnancy rate was higher than the average annual calving rate at ~37% and ~23% respectively. Together, these data suggest that the declines in reproductive success could be, at least in part, the result of females being unable to accumulate the energy reserves necessary to maintain pregnancy and/or meet the energetic demands of lactation in years of poorer prey availability rather than solely an inability to become pregnant. The decline in calving rates over a period of major environmental variability may suggest that this population has limited resilience to such ecosystem change.

The 2019 PGDIS position statement on transfer of mosaic embryos within a context of new information on PGT-A.

BACKGROUND: A recently published Position Statement (PS) by the Preimplantation Genetics Diagnosis International Society (PGDIS) regarding utilization of preimplantation genetic testing for aneuploidy (PGT-A) in association with in vitro fertilization (IVF) contained inaccuracies and misrepresentations. Because opinions issued by the PGDIS have since 2016 determined worldwide IVF practice, corrections appear of importance. METHODS: The International Do No Harm Group in IVF (IDNHG-IVF) is a spontaneously coalesced body of international investigators, concerned with increasing utilization of add-ons to IVF. It is responsible for the presented consensus statement, which as a final document was reached after review of the pertinent literature and again revised after the recent publication of the STAR trial and related commentaries. RESULTS: In contrast to the PGDIA-PS, we recommend restrictions to the increasing, and by IVF centers now often even mandated, utilization of PGT-A in IVF cycles. While PGT-A has been proposed as a tool for achieving enhanced singleton livebirth outcomes through embryo selection, continued false-positive rates and increasing evidence for embryonic self-correction downstream from the testing stage, has led IDNHG-IVF to conclude that currently available data are insufficient to impose overreaching recommendations for PGT-A utilization. DISCUSSION: Here presented consensus offers an alternative to the 2019 PGDIS position statement regarding utilization of preimplantation genetic testing for aneuploidy (PGT-A) in association with in vitro fertilization (IVF). Mindful of what appears to offer best outcomes for patients, and in full consideration of patient autonomy, here presented opinion is based on best available evidence, with the goal of improving safety and efficacy of IVF and minimizing wastage of embryos with potential for healthy births. CONCLUSIONS: As the PGDIS never suggested restrictions on clinical utilization of PGT-A in IVF, here presented rebuttal represents an act of self-regulation by parts of the IVF community in attempts to control increasing utilization of different unproven recent add-ons to IVF.

Single and double embryo transfer provide similar live birth rates in frozen cycles.

Research question: Do live birth rates (LBRs) differ in frozen cycles of women who received single versus double embryo transfer?Design: Retrospective cohort study including women who underwent their first frozen embryo transfer (FET) in a tertiary referral University Hospital between 2009-2014.Results: 3601 patients were included in the analysis with 1936 (53.8%) having a single embryo transfer (SET) and 1665 (46.2%) having a double embryo transfer (DET). Overall, 657/3601 (18.24%) had a live birth. LBR were similar between SET and DET either for cleavage [100/757 (13.1%) versus 153/1032 (14.8%), p = .33] or blastocyst stage FET [256/1179 (21.7%) versus 148/633 (23.4%), p = .4). Ongoing pregnancy rates were comparable between DET and SET [316/1665 (18.9%) versus 359/1936 (18.5%)]. Multiple delivery rates were significantly higher in women with DET compared to SET [53/316 (16.7%) versus 7/359 (1.9%), p < .001]. Multivariate logistic regression analysis allowing adjustment for relevant confounders showed that the number of embryos transferred in the frozen cycle was not related to LBR.Conclusions: This is the largest study providing evidence that both SET and DET may result in similar LBR, albeit multiple pregnancy rates are significantly lower in case of SET. Therefore, SET should be the main strategy in women undergoing FET.

Dydrogesterone-primed ovarian stimulation is an effective alternative to gonadotropin-releasing hormone antagonist protocol for freeze-all cycles in polycystic ovary syndrome.

OBJECTIVE: To compare the effects of progestin-primed ovarian stimulation using dydrogesterone (DYD) and a gonadotropin-releasing hormone (GnRH) antagonist protocol on cycle characteristics and pregnancy rates in freeze-all cycles in patients with polycystic ovary syndrome (PCOS). METHODS: Medical records of PCOS patients who underwent freeze-all in vitro fertilization cycles between April 2017 and April 2019 at the Novafertil in vitro fertilization Center were retrospectively evaluated. The primary outcome measure was the incidence of premature luteinizing hormone surge. Secondary outcome measures were the total number of mature oocytes retrieved, fertilization rate, clinical pregnancy rates and ongoing pregnancy rates. RESULTS: A total of 525 patients were included in the study. DYD-primed ovarian stimulation and a GnRH antagonist protocol were applied in 258 and 267 patients, respectively. The baseline parameters were similar between the two groups. The numbers of mature and fertilized oocytes were similar in the cetrorelix (CET) group and DYD group (11.43 ± 3.48 vs. 11.29 ± 4.34, respectively, P = 0.692; and 8.98 ± 2.93 vs. 8.62 ± 3.67, respectively, P = 0.208). Premature luteinization was rare in both groups, and the difference between the groups was not statistically significant (2.9% vs. 1.5%, respectively, P = 0.268). There was no significant difference in clinical pregnancy rate of the first frozen embryo transfer cycle between the DYG group and the CET group (56% [120/214] vs. 55.6% [113/203], respectively, P = 0.283). There were no significant differences in biochemical pregnancy rates, implantation rates, miscarriage rates or ongoing pregnancy rates between the two groups (P > 0.05). CONCLUSION: Dydrogesterone-primed ovarian stimulation seems to be an effective alternative to the GnRH antagonist protocol for freeze-all cycles in PCOS patients.

Comparison of two different oocyte vitrification methods: a prospective, paired study on the same genetic background and stimulation protocol.

STUDY QUESTION: Can two different methods for oocyte vitrification, one using an open tool and the other a closed tool, result in similar oocyte survival rates? SUMMARY ANSWER: The oocyte survival rate was found to be higher in the closed method. WHAT IS KNOWN ALREADY: Open vitrification is performed routinely in oocyte donation cycles. Closed oocyte vitrification may result in slower cooling rates and thus it is less used, even though it has been recommended in order to avoid the risk of cross-contamination between material from different patients. STUDY DESIGN, SIZE, DURATION: This is a prospective cohort study with sibling oocytes carried out in a fertility center between July 2014 and January 2016. The study included 83 oocyte donors each providing a minimum of 12 mature oocytes (metaphase II: MII) at oocyte retrieval. Oocyte survival rate and fertilization rate, as well as reproductive outcomes (biochemical, clinical, ongoing pregnancy and live birth rates) per embryo transfer and also cumulatively between the two methods were compared by Chi2 tests. PARTICIPANTS/MATERIALS, SETTING, METHODS: Donor oocytes were denuded and six MII oocytes from each donor were vitrified using an open method and later assigned to one recipient, while another six MII oocytes were vitrified using a closed method and assigned to a different recipient (paired analysis). ICSI was used in all cases and embryo transfer was performed on Day 2-3 in all cases. MAIN RESULTS AND THE ROLE OF CHANCE: Oocyte donors were 24.8 years old on average (SD 4.7). Recipient age (average 41.2 years, SD 4.7) and BMI (mean 23.8 kg/m2, SD 4.0) were similar between recipient groups. Oocytes vitrified using the closed method had higher survival rate (94.5% versus 88.9%, P = 0.002), but lower fertilization rate (57.1% versus 69.8%, P < 0.001) compared to the open method. The number of fresh embryos transferred in the two groups was 1.8 on average (SD 0.4). Biochemical (45% closed versus 50% open), clinical (40% versus 50%) and ongoing (37.5% versus 42.5%) pregnancy rates were not different between groups (P > 0.05) and neither were live birth rates (37.5% versus 42.5%, P > 0.05). Cumulative reproductive results (obtained after the transfer of all the embryos) were also similar between groups. LIMITATIONS, REASONS FOR CAUTION: The participants of this study were oocyte donors, i.e. young women in good health, and care should be exerted in extending our results to other populations such as infertility patients, oncofertility patients and women freezing oocytes to delay childbearing. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that, in spite of different survival and fertilization rates, closed and open oocyte vitrification methods should offer similar reproductive outcomes up to cumulative live birth rates. STUDY FUNDING/COMPETING INTEREST(S): The authors report no conflict of interest. Vitrolife provided the media and the closed method tool needed for the study at no cost.

Elective Single Embryo Transfer in the Setting of Funded In Vitro Fertilization: Two Years' Experience in an Ontario Hospital-Based Fertility Clinic.

OBJECTIVE: The objective of this study was to assess data from a fertility clinic and identify differences in patient and cycle characteristics, clinical pregnancy rates, and multiple gestation rates before and after fertility treatment funding and a policy of elective single embryo transfer were instituted by the Ontario government to reduce multiple gestations arising from fertility treatment. METHODS: This study was a retrospective database review of clinic and embryology laboratory data for all patients undergoing in vitro fertilization (IVF) and intracytoplasmatic sperm injection (ICSI) cycles over a 4-year period. The investigators compared IVF and ICSI cycles before funding, from January 1, 2014 to December 31, 2015, with cycles after funding, from January 1, 2016 to December 31, 2017. RESULTS: The number of cycles performed over a 2-year period increased from 554 to 853, of which 76.2% were funded. Patient age, body mass index, and parity were similar before and after funding. Fewer patients receiving funded IVF or ICSI had had a previous cycle. Cycle cancellation rates were similar before and after funding; however, there were fewer embryo transfers per cycle start after funding (80.3% vs. 72.2%, P = 0.001). The clinical pregnancy rate was similar before and after funding (37.8% vs. 32.5%, P = 0.09), whereas the multiple gestation rate was significantly lower (13.1% vs. 3.5%, P = 0.001). CONCLUSION: Since the government of Ontario began funding IVF and ICSI cycles, more patients are accessing treatment, many for the first time. The clinical pregnancy rate was maintained, whereas multiple gestations were significantly reduced. These findings support the benefit of single embryo transfer in the context of funded IVF and ICSI and demonstrate the importance of government-funded assisted reproductive technology.

Reproductive efficiency in naturally serviced and artificially inseminated beef cows.

A study was conducted to compare conception rates in 71 Tuli and 86 Afrikander beef cattle bred using either artificial insemination (AI) or the bull. Animals were bred using either artificial insemination or natural service at Matopos Research Station. Animals were grouped into three groups of heifers (parity 0; P0), second calvers (parity 1; P1) and mature cows (parity 2; P2) before being randomly assigned to one of the two breeding methods. A binary logistic regression was used for statistical analysis where breeding method (AI vs natural service) was the treatment factor and conception rate was the measured response while breed, parity and last calving date were non-treatment factors. No significant differences were observed in conception rates between breeds (P > 0.05). However, the method of breeding animals, parity and calving interval affected (P < 0.05) conception rates. The breeding method, parity and calving interval had a positive Kendall's tau-b correlation coefficients to conception. More animals were pregnant when AI (77.6%) was used compared with natural mating (56.79%). Conception rates were significantly lower (P < 0.05) in C1 compared with C2 cattle. The odds ratio for breeding method and parity are positive and significant (P < 0.05). In conclusion, the study confirms that artificial inseminated animals had similar conception rates to naturally serviced animals for both Tuli and Afrikander breeds. As such, artificial insemination technology can be used to complement or substitute natural service in indigenous cattle's of Zimbabwe.