Post-oocyte Retrieval Research Articles

Efficacy analysis of letrozole combined with gonadotropin-releasing hormone antagonists in patients with high risk of ovarian hyperstimulation syndrome undergoing total embryo freezing

Objective: To investigate the clinical efficacy of letrozole combined with gonadotropin-releasing hormone antagonists (GnRH-ant) in patients at high risk of ovarian hyperstimulation syndrome (OHSS) who underwent total embryo freezing after oocyte retrieval. Methods: A retrospective analysis was conducted on 348 female patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at the Reproductive and Genetic Hospital of the First Affiliated Hospital of Zhengzhou University between January and July 2023. Due to their high risk of OHSS, these patients canceled fresh embryo transfer and opted for total embryo freezing. Based on patients' preferences, those who received GnRH-ant and letrozole after oocyte retrieval were categorized as the intervention group (164 cases), while those who did not receive these medications were categorized as the control group (184 cases). The first luteal phase after oocyte retrieval, OHSS grading, ovarian volume, and estradiol (E2) levels were evaluated in both groups. A multivariate logistic regression model was used to analyze factors related to moderate-to-severe OHSS among patients at high risk of OHSS who underwent total embryo freezing after oocyte retrieval. Results: The age of the intervention and control groups was (29.3±3.8) and (29.4±4.1) years, respectively (P=0.821). The duration of the first luteal phase post-oocyte retrieval was shorter in the intervention group [(7.16±1.39) days] compared to that in the control group [(13.88±2.11) days] (P<0.001). The incidences of mild, moderate, and severe OHSS in the intervention group were 75.0% (123 cases), 23.8% (39 cases), and 1.2% (2 cases), respectively, whereas in the control group they were 12.5% (23 cases), 60.9% (112 cases), and 26.6% (49 cases) (P<0.001). E2 levels on the 2nd and 6th days after oocyte retrieval [M(Q1,Q3)] in the intervention group were 1 520.0 (1 213.8, 1 884.8) and 108.5 (45.6, 218.0) ng/L, respectively, which were statistically significantly lower than those in the control group [1 666.0 (508.8, 1 702.0) ng/L] and [1 761.0 (826.0, 2 546.5) ng/L] (P<0.001). The abdominal cavity effusion in the intervention group [M(Q1,Q3)] were 19.5 (0, 30) and 0 mm, statistically significantly less than those in the control group [46.0 (0, 61.0) mm] and [54.5 (0, 69.5) mm] (P<0.001). On the 6th day after oocyte retrieval, the bilateral ovarian volumes in the intervention group were smaller than those in the control group (P<0.001). Multivariate logistic regression analysis indicated that no combined treatment with letrozole and GnRH-ant was a risk factor of moderate to severe OHSS. The risk of developing moderate to severe OHSS in the control group was 35.312 times higher than that in the intervention group (OR=35.312, 95%CI: 17.488-71.300). Conclusions: The administration of letrozole combined with GnRH-ant post-oocyte retrieval in patients at high risk of OHSS can prevent the occurrence of moderate-to-severe OHSS, shorten the first luteal phase, accelerate the reduction of serum E2 levels, and promote the recovery of ovarian volume and absorption of abdominal fluid.

P-251 Denudation time is crucial to increase the proportion of top-quality embryos in egg donation cycles

Abstract Study question How do different denudation times affect in the efficiency of the egg donation cycles? Summary answer Undetected in vitro matured oocytes, resulting from delayed denudations, contribute to a decreased top-quality blastocyst ratio. What is known already While the timeframe for sperm microinjection in ICSI cycles is widely agreed upon (2-6 hours post-oocyte retrieval), no definitive denudation time preference has been established. Published studies diverge on the advantages of early or late denudation, assessing the impact of trigger-to-denudation time (T-D time) on oocyte maturation. Advocates of early denudation contend it prevents oocyte aging, reducing in vitro culture and enhancing outcomes. These studies, often using data from cycles with own oocytes, exhibit high variability and inconsistent conclusions. The present work introduces an alternative hypothesis on the benefits of early denudation, employing a more stable study model. Study design, size, duration This retrospective study encompasses oocyte donation cycles, employing a short antagonist protocol and ovum pick-up 35.5 hours post-trigger, conducted from January 2019 to July 2023 including 1,559 stimulations. Additionally, 1,275 ICSI cycles without detected sperm pathologies derived from these stimulations were examined to evaluate the influence of T-D time on the reproductive outcomes. Six comparable groups were established by segmenting the sample according to T-D time, annotated in 30-minute intervals (36.5h to 39h). Participants/materials, setting, methods Rates of MII, MI, and nonviable oocytes were examined among 1,559 stimulations resulting in 29,671 oocytes (36.5h:187-stimulations/3,178-oocytes; 37h:226/3,836; 37.5h:614/11,921; 38h:329/6,884; 38.5h:119/2,322; 39h:84/1,530). Additionally, in 1,275 ICSI cycles involving 11,333 MII-oocytes (36.5h:117-ICSI cycles/1,027-MII; 37h:130/1,133; 37.5h:502/4,426; 38h:316/2,925; 38.5h:120/1,041; 39h:90/781), comparisons were made for fertilization, abnormal fertilization, ICSI degeneration, useful day 5/6 blastocyst (transferred or cryopreserved; &amp;gt;3BB-top and ≤3BB-good quality by Gardner score), pregnancy, and live birth rates. Statistics were ANOVA, Chi-square test and Pearson’s correlation. Main results and the role of chance Oocyte maturation profile assessment reveals that groups with later denudation exhibit a higher proportion of MII-oocytes (36.5h:80.71%; 37h:81.04%; 37.5h:81.26%; 38h:80.83%; 38.5h:84.84%; 39h:85.29%; r:0.8475; p &amp;lt; 0.05), reaching significance from 38.5h onward (p &amp;lt; 0.05). This is complemented by a strong negative correlation between T-D time and MI rate (36.5h:5.51%; 37h:5.32%; 37.5h:4.64%; 38h:4.17%; 38.5%h:3.27%; 39h:2.94%; r:-0.9881; p &amp;lt; 0.05), with significant declines at 38h and 38.5h (p &amp;lt; 0.05). No correlation between useless oocytes proportion and T-D time was observed (r:-0.5983; p = 0.21). This illustrates that certain MI-collected oocytes progressively mature during in vitro culture and subsequently, upon denudation, are classified as MII. This overestimates in vivo-matured oocytes. No differences attributed to T-D time were observed regarding fertilization, abnormal fertilization, or ICSI degeneration rates. While time does not affect the rate of useful embryos achieved (36.5h:49.4%; 37h:46.4%; 37.5h:44.6%; 38h:48.0%; 38.5h:50.6%; 39h:47.2%; r:0.1342; p = 0.80), it has an impact on the blastocysts quality. The proportion of top-quality blastocysts (&amp;gt;BB) progressively decreases with T-D time (36.5h:86.2%; 37h:85.2%; 37.5h:85.4%; 38h:81.2%; 38,5h:80.5%; 39h:80.5%; r:-0.925; p &amp;lt; 0.05). Out of 1,794 single embryo transfers, 1,477 have conclusive outcome. No implication of T-D time was detected in pregnancy rate (36.5h:59.88%; 37h:64.07%; 37.5h:61.54%; 38h:65.02%; 38.5h:59.55%; 39h:62.26%; r:0.0489; p = 0.93) or live birth rate (36.5h:40.31%; 37h:51.85%; 37.5h:39.12%; 38h:45.04%; 38.5h:41.83%; 39h:37.96%; r:-0.375; p = 0.46). Limitations, reasons for caution This study has inherent limitations as a retrospective analysis. Additionally, the potential effects of a denudation earlier than 36.5 hours post-trigger, not yet standardized in the laboratory, were not assessed. Wider implications of the findings Delayed denudation may benefit autologous IVF by fostering in vitro oocyte maturation. In egg donation cycles, early denudation is preferable for stringent selection of in vivo matured oocytes, yielding superior results. Additionally, shortening or eliminating incubation periods would enhance the automated sequence of diverse processes during an IVF cycle. Trial registration number not applicable

P-729 Contribution of medical-administrative databases to health monitoring: example of ovarian hyperstimulation syndrome (OHSS)

Abstract Study question Can we monitor post-oocyte retrieval ovarian hyperstimulation syndrome (OHSS) in the French national health data system to complement the French ART vigilance system? Summary answer Medico-administrative databases offer a more comprehensive view of post-oocyte retrieval complications and can be used to detect abnormal increases in frequency and outlier ART centers. What is known already Assisted reproductive technology (ART), widely used in Europe, accounts for about 3% of births in France. The various studies of ART complications are reassuring, showing relatively low overall complication rates. Nonetheless, the European Union has established a vigilance system to monitor these complications. However, this system is not an exhaustive source of information and does not provide a complete overview of post-ART complications. Study design, size, duration The study population was identified from the comprehensive French National Hospital discharge database and included 53,490 women under 46 years old who underwent 65,924 oocyte retrievals in 2022. Women were classified into three population subgroups according to the indication of oocyte retrieval: infertility (IF), fertility preservation (FP), and oocyte donation (OD). Participants/materials, setting, methods Hospital stays for OHSS within two months post-retrieval were analyzed and characterized according to various characteristics (age, comorbidities, indication of oocyte retrieval, type of hospital stay, length of hospital stay...). Multivariate analysis was performed to determine the relation between the occurrence of OHSS and women’s characteristics, and results are expressed as odds ratios (ORs) and 95% CI. A funnel plot was used to compare the OHSS rate per center with the national average. Main results and the role of chance Hospitalized OHSS accounted for 1.1% of retrievals in 2022 (n = 718). The mean age of the women was 31.6 years (SD 4.5). Women with Polycystic Ovary Syndrome (PCOS) accounted for about 4% of the women with OHSS. More than half of OHSS hospital stays lasted less than two days (54%). Of these stays, 2% of women were in intensive care. Multivariate analysis showed a significantly higher OHSS risk in women under 30 and those with PCOS. Other risk factors are currently introduced into the model, such as a history of OHSS or pregnancy. Funnel plot analysis showed that one ART center has an OHSS rate significantly higher than the national average. In the centers that stand out from all the others, the objective is to return to these centers to understand the possible reasons for this observed rate and to implement corrective measures. Limitations, reasons for caution Despite all its advantages, the French national health data system presents some limitations, such as the risk of inappropriate coding. Moreover, the unavailability of personal or clinical information prevented us from considering certain risk factors. Wider implications of the findings Despite the limits of using medico-administrative databases, this approach provides a better representation of post-ART complications and is a promising way to complement the ART vigilance reporting system. This concept will also be generalized to other complications with regular feedback to professionals. Trial registration number not applicable

P-242 ICSI, the sooner, the better

Abstract Study question What is the impact of different ICSI timing on the efficiency of egg reception cycles concerning both denudation and trigger events? Summary answer The interval between denudation and ICSI significantly compromises cycle efficiency, particularly blastocyst quality. Delayed ICSI impairs this impact relative to the trigger event. What is known already The established consensus on the optimal ICSI timeframe, spanning 2-6 hours post-oocyte retrieval, has been extensively documented. However, the acknowledged variability within this window has prompted a critical review. Recent studies highlight the need for a more nuanced understanding, suggesting that phenomena affecting ICSI outcomes can be better elucidated by adopting stable models such as oocyte reception cycles. By removing the oocyte factor, these models offer a more precise perspective, addressing the temporal intricacies integral to successful ICSI procedures. The present research underscores the imperative of refining the temporal dimension for optimal reproductive results. Study design, size, duration This retrospective study encompassed 1,275 egg reception ICSI-cycles conducted between January 2019 and July 2023. Donors underwent stimulation using a short antagonist protocol, and oocytes were collected 35.5h post-trigger. The impact of both, the time between denudation-ICSI (D-ICSI time) and the time between trigger-ICSI (T-ICSI time) on reproductive outcomes were analysed. Six comparable groups were established by 30-minute intervals, segmenting the sample based on D-ICSI time (0.5h to 3h) and T-ICSI time (38h to 40.5h). Participants/materials, setting, methods A total of 1,275 cycles, involving 11,333 MII-oocytes, were stratified based on D-ICSI time (0.5h:89-cycles/761-MII; 1h:128/1,186; 1.5h:269/2,385; 2h:270/2,415; 2.5h:340/3,064; 3h:179/1,522) and T-ICSI time (38h:183/1,631; 38.5h:131/1,158; 39h:246/2,205; 39.5h:219/1,952; 40h:173/1,534; 40.5h:323/2,853). Comparative analyses were conducted for fertilization, abnormal fertilization, ICSI degeneration, and useful day 5/6 blastocyst outcomes (transferred or cryopreserved; &amp;gt;3BB-top and ≤3BB-good quality by Gardner score), as well as pregnancy and live birth rates (1,594 SET). Statistical methods employed included ANOVA, Chi-square tests, and Pearson’s correlation. Main results and the role of chance Several parameters showed stability across different time intervals of D-ICSI time: fertilization (0.5h:74.6%; 1h:72.6%; 1.5h:74.0%; 2h:75.9%; 2.5h:74.8%; 3h:74.4%; r = 0.3707; p = 0.469), blastocyst (0.5h:65.3%; 1h:62.6%; 1.5h:61.7%; 2h:60.1%; 2.5h:64.8%; 3h:63.8%; r= -0.068; p = 0.898), and live birth rates (0.5h:39.5%; 1h:35.9%; 1.5h:36.6%; 2h:40.2%; 2.5h:39.9%; 3h:39.7%; r = 0.474; p = 0.342). However, an extended interval significantly correlated with increased oocyte ICSI-degeneration (0.5h:5.5%; 1h:6.7%; 1.5h:6.7%; 2h:6.5%; 2.5h:7.4%; 3h:8.5%; r = 0.903; p &amp;lt; 0.05) and a decreased proportion of top-quality blastocysts (0.5h:86.8%; 1h:89.2%; 1.5h:86.4; 2h:85.3%; 2.5h:81.2%; 3h:75.2%; r= -0.879; p &amp;lt; 0.05). Extended culture of cumulus cell-free oocytes may promote oocyte aging and, consequently, compromise optimal development (consistent with findings in other studies). In evaluating T-ICSI time, similar trends to those observed in D-ICSI time persist in fertilization (r = 0.275, p = 0.598), blastocyst (r = 0.233, p = 0.657), live birth (r = 0.516, p = 0.295), and ICSI-degeneration rates (r = 0.864, p &amp;lt; 0.05). The negative correlation in the quality of generated useful blastocysts significantly intensifies (38h:90.6%; 38.5h:87.5%; 39h:84.7%; 39.5h:82.4%; 40h:80.1%; 40.5h:79.7%; r= -0.982, p &amp;lt; 0.05). In a separate analysis, we observed that undetected in vitro matured oocytes, stemming from delayed denudations, lead to a reduction in the top-quality blastocyst ratio. This concept, along with D-ICSI time, seems to synergize, emphasizing the adverse trend when evaluating blastocyst qualities concerning T-ICSI times. Limitations, reasons for caution This study has inherent limitations as a retrospective analysis. Additionally, the potential effects of ICSI earlier than 0.5 hours post denudation and 38 hours post-trigger, not yet standardized in the laboratory, were not assessed. Wider implications of the findings Extended incubation of denuded and non-injected oocytes fosters oocyte aging. Consequently, cycle efficiency is compromised with prolonged incubation times. The reduction of these times holds promise for improving the efficiency of IVF treatments. Additionally, shortening or eliminating incubation periods would enhance the automated sequence of diverse processes during an IVF. Trial registration number not applicable

Efficacy of Dan'e Fukang Soft Extract in Moderate Ovarian Hyperstimulation Syndrome for Concurrent Treatment of Blood and Fluid Guided by the "Triple Prevention" Principle.

This study aimed to evaluate the therapeutic efficacy and safety of Dan'e Fukang soft extracts in moderate ovarian hyperstimulation syndrome (OHSS) for the simultaneous treatment of blood and fluid, guided by the traditional Chinese medicine principle of "triple prevention". This study conducted a retrospective analysis of clinical data from outpatients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection embryo transfer (ICSI-ET). A total of 2245 cases were included and divided into a treatment group (1002 cases) and a control group (1243 cases). Patients in the treatment group were administered Dan'e Fukang soft extracts orally in addition to conventional Western medicine. Comparative assessments were made between the two groups on pelvic ascites volume, maximum ovary diameter, dysmenorrhea incidence post-oocyte retrieval, and safety indicators. There were no statistically significant differences between the treatment group and the control group in terms of general characteristics or the levels of follicle-stimulating hormone (FSH), luteotropic hormone (LH), estradiol (E2), or progesterone (P) at the time of gonadotropin (Gn) initiation. The groups did not differ significantly when we compared the levels of LH, E2, or P on the day of human chorionic gonadotropin (hCG) injection and during ovarian hyperstimulation protocols (P > 0.05 for all indicators). The differences in the volume of pelvic ascites, the maximum ovarian diameter, and the incidence of dysmenorrhea after oocyte retrieval were statistically significant between the treatment group and the control group (P < 0.05 in both). There were no instances of adverse reactions in either group. Based on the traditional Chinese medicine principle of "triple prevention", the use of Dan'e Fukang soft extracts for the simultaneous treatment of blood and fluid in moderate OHSS significantly improved the absorption of pelvic ascites, promoted ovarian recovery, and reduced the incidence of dysmenorrhea after oocyte retrieval.

Contribution of medico-administrative databases to health vigilance: example of post-oocyte retrieval infections.

Can we monitor post-oocyte retrieval infections in the French national health data system to complement the French ART vigilance system? Medico-administrative databases provide a more comprehensive view of post-oocyte retrieval infections and can be used to detect abnormal increases in frequency and outlier ART centers as a complementary tool to the ART vigilance system. The various studies of ART complications are reassuring, showing relatively low overall complication rates. Nonetheless, the European Union has set up a vigilance system to monitor these complications. However, this system is not an exhaustive source of information and does not provide a complete overview of post-ART complications. The study population was identified from the comprehensive French national hospital discharge database. It included women under 46 years of age undergoing an oocyte retrieval in 2019, classified into three population subgroups according to the indication of oocyte retrieval: infertility (IF) , fertility preservation (FP), and oocyte donation (OD) . The study population included 52 098 women who had undergone 65 948 oocyte retrievals in 2019. Hospital stays and delivery of antibiotics within 31 days after oocyte retrieval were analyzed. Women and infections were characterized according to various characteristics (age, comorbidities, indication of oocyte retrieval, type of hospital stay, length of hospital stay, type of antibiotherapy, etc.). Multivariate analysis was performed to determine the relation between the occurrence of infection and women's characteristics, and results are expressed as odds ratios (ORs) and 95% CI. A funnel plot and a box plot were used to compare the infection rate per center with the national average and to detect outliers. Infections in the month following the oocyte retrieval represented 6.9% of the procedures in 2019 (n = 4522). Of these infections, 112 were hospitalized (0.2% of oocyte retrievals), and 4410 were non-hospitalized (6.7% of oocyte retrievals). The hospitalized infections were essentially gynecological infections (40.9%) and urinary tract infections (23.5%). In 87.9% of non-hospitalized infections, a single antibiotic therapy was prescribed. Mixed-effect model analysis showed that the risk of infection was significantly higher in women under 30 years of age, in the FP population, in supplementary universal health coverage (CMU-C) beneficiaries, and women with endometriosis. Funnel plot and box plot analysis showed that three ART centers have an infection rate significantly higher than the national average. In the three centers that stand out from all the others, the objective is to return to these centers to understand the possible reasons for this observed rate and to implement corrective measures. Despite all its advantages, the French national health data system presents some limitations, such as the risk of inappropriate coding. Another limitation of this study is that we cannot confirm an attributable relation between the infection and the ART procedure, even if the delay of 31 days after oocyte retrieval is consistent with the occurrence of a post-retrieval complication. In addition, antibiotics may be prescribed as a 'precautionary' measure in certain situations (women with a susceptibility to infection, complicated procedures), or as antibiotic prophylaxis for embryo transfer. Despite the limits in identifying post-ART infections in medico-administrative databases, this approach is a promising way to complement the ART vigilance reporting system. This concept developed for infections will also be generalized to other complications with regular feedback to professionals. No specific funding was sought for the study. The study was supported by the Agence de la biomédecine, France. The authors declare that they have no conflict of interest. N/A.

Remote IVF: a clinical and laboratory guide to performing remote oocyte retrievals.

The aim of this guide is to describe different scenarios when remote IVF would be needed, considerations around how to plan for the procedure, proper equipment in the procedure room, and proper transportation of oocytes from the procedure room. There are two different scenarios for remote IVF: (1) IVF clinics designed knowing the embryology laboratory is nonadjacent and (2) IVF clinics that routinely provide care to patients in their clinic and want to provide care to those who are ineligible for a retrieval under anesthesia in an outpatient facility. This guide will focus on both scenarios. Much of the advice can be used for IVF clinics that routinely perform oocyte retrievals nonadjacent to their embryology laboratories. Special considerations are needed when patients with complex comorbidities require high-level of care and hospital-level monitoring while under anesthesia and/or post-oocyte retrieval, and are thus unable to be treated in the standard facility. For these reasons we have created a comprehensive guide to nonadjacent, or off-site, oocyte retrievals for reproductive endocrinology and infertility (REI) physicians, nurses, and embryologists to use when planning care for IVF patients. Going forward, we will refer to both these scenarios as remote IVF.

The Timing of Intracytoplasmic Sperm Injection Relative to Oocyte Retrieval: A Systematic Review and Meta-Analysis

Background: It is currently inconclusive whether different intracytoplasmic sperm injection (ICSI) timings post oocyte retrieval (POR) lead to altered chance of clinical pregnancy and live birth following in vitro fertilization (IVF) treatment. This study, therefore, aimed to synthesize literature-based evidence for better clinical guidance regarding ICSI practice. Methods: A systematic review and meta-analysis were performed according to PRISMA guidelines. Studies were searched for in PubMed, MEDLINE, EMBASE, and the Cochrane Library. Outcome endpoints included clinical pregnancy and live birth rates (LBRs). Results: A total of 605 records were retrieved in the initial search. After exclusion, 30 articles were included for further screening for eligibility. For meta-analysis, 1 prospective and 5 retrospective cohort studies were included for pooled analysis, from which clinical pregnancy rates (CPRs) were evaluated in 6 studies while LBRs were evaluated in 3 studies. CPRs were comparable when ICSI was performed at (a) [Formula: see text] hours POR (risk ratio or RR = 1.00, [Formula: see text] confidence interval [CI] 0.94–1.08) vs [Formula: see text] hours, (b) [Formula: see text] hours (RR = 1.01, [Formula: see text] CI 0.88–1.16) vs [Formula: see text] hours, (c) [Formula: see text] hours (RR = 0.99, [Formula: see text] CI 0.93–1.05) vs [Formula: see text] hours, (d) [Formula: see text] hours (RR = 0.98, [Formula: see text] CI 0.93–1.02) vs [Formula: see text] hours, and (e) [Formula: see text] hours (RR = 1.05, [Formula: see text] CI 0.90–1.23) vs [Formula: see text] hours. However, LBR was reduced when ICSI was performed [Formula: see text] hours POR vs [Formula: see text] hours (RR = 0.94, [Formula: see text] CI 0.89–0.99), but such reduction disappeared when comparing [Formula: see text] hours POR (RR = 1.09, [Formula: see text] CI 0.85–1.38) vs [Formula: see text] hours. Conclusions: CPRs remain comparable when ICSI is performed at a range of timings up to 6-hour POR. However, LBR may benefit slightly by scheduling ICSI between 5- and 6-hour POR.

Is there an optimal window of time for transferring single frozen-thawed euploid blastocysts? A cohort study of 1170 embryo transfers.

Is there an optimal window of time when the transfer of single frozen-thawed euploid blastocysts is associated with a maximal live birth rate (LBR)? Performing a single frozen-thawed euploid blastocyst transfer at 160 ± 4 h post-hCG trigger in modified-natural frozen-thawed embryo transfer (FET) cycles was independently associated with a higher LBR as compared to transfers outside this window; however, in natural FET cycles, LBRs were comparable across a wider range of time intervals. There is compelling evidence for maintaining embryo-endometrial synchrony to optimize clinical outcomes following FETs, which could potentially be achieved by matching the transfer time of an embryo post-ovulation to its developmental age post-oocyte retrieval. For modified-natural cycles, ovulation is widely accepted to occur ∼40 h following the hCG trigger, whilst ovulation following spontaneous LH surge onset is thought to vary from 24 to 56 h. This is a multicentered retrospective cohort study analyzing 1170 single frozen-thawed euploid blastocyst transfers following trophectoderm biopsy and preimplantation genetic testing (PGT) between May 2015 and February 2019. Limiting the analysis to single euploid embryo transfers allowed for a more accurate estimation of the endometrial synchrony factor by controlling for the developmental stage of the embryo (full blastocyst or more advanced) and its genetic composition. LBR per FET was the primary outcome measure. Patients underwent natural or gonadotrophin-induced preparation of the endometrium, with serial serum oestradiol, LH and progesterone measurements. Optimally timed transfers were predefined as those conducted 120 ± 4 h post-ovulation since biopsy and subsequent cryopreservation of full blastocysts which is usually performed at 116-124 h post-oocyte retrieval. This was considered the equivalent of 160 ± 4 h post-hCG trigger in modified-natural cycles (n = 253), as ovulation was assumed to occur ∼40 h after the hCG trigger. For natural cycles (n = 917), this was also considered to be, on average, 160 ± 4 h post the spontaneous LH surge. Thus, study groups were determined as those with optimal timing or not, and additional exploratory and subgroup analyses were performed, varying the time window in terms of onset and width, both overall and per endometrial preparation protocol. Statistical analysis was performed using the generalized estimating equations (GEE) framework to control for the clustered nature of the data while adjusting for potential confounders. Overall, LBRs were significantly higher when the transfer had been performed at 160 ± 4 h post-hCG trigger or LH surge onset compared to when it had been performed outside this window (44.7% vs 36.0%; P = 0.008). A multivariable regression GEE model including the cycle type (natural versus modified-natural), previtrification embryo quality (top versus good quality), embryo stage (fully hatched versus hatching or earlier blastocyst), vitrification day (D5 versus D6) and survival rate (>90% versus <90%) as covariates, confirmed that, overall, embryo transfers conducted 160 ± 4 h post-hCG trigger or LH surge onset (the assumed equivalent of 120 ± 4 h post-ovulation) were associated with a significantly higher LBR (relative risk (RR) 1.21, 95% CI 1.04-1.41). Subgroup exploratory analyses per endometrial preparation protocol demonstrated that these findings were primarily present in the modified-natural cycle group (RR 1.52, 95% CI 1.15-1.99), whilst the natural cycle group showed comparable LBRs across a wider range of time intervals. Moreover, the overall LBR for the natural group (36.8%; 95% CI 33.7-39.9%) was lower than that of the modified-natural group (41.3%; 95% CI 35.4-47.1%), suggesting that there likely remains a greater potential to further optimize the timing of natural cycle embryo transfers. As with all retrospective studies, the presence of residual unknown bias cannot be excluded. Additionally, patients included in this study were a selected group who underwent PGT for specific reasons and hence the results obtained might not be directly applicable to the general population or embryos that have not undergone embryo biopsy. Furthermore, the criteria utilized to interpret hormonal data from natural cycles were specifically adopted for the present study and need to be validated in further studies. The results of this study highlight the significance of embryo-endometrial synchrony for the optimization of frozen embryo transfer outcome. However, it also clearly supports that the implantation window is in most cases wide and the achievement of live birth is possible with relatively high success rates even outside the optimal window of 160 ± 4 h post-trigger for modified-natural cycles and across a range of time intervals for natural cycles. Additionally, this study suggests that implantation rates could be further optimized in natural cycles by improving methods of assessing embryo-endometrial synchrony. C. V. is supported by a National Health and Medical Research Council Early Career Fellowship (GNT1147154). No other funding was received for this study and there are no competing interests. N/A.

P-203 Searching for the optimal timing of intracytoplasmic sperm injection post oocyte retrieval: a systematic review and meta-analysis

Abstract Study question What is the optimal time post oocyte retrieval (POR) to undertake intracytoplasmic sperm injection (ICSI) in order to maximise subsequent pregnancy and live birth outcomes? Summary answer Delaying ICSI for 5 hours or more POR may compromise subsequent clinical pregnancy and live birth rates. What is known already It is often challenging to perform ICSI at a set timing POR, especially in ART clinics with a heavy workload. However, the degree of flexibility in ICSI timing remains unclear in the literature. Some articles have reported detrimental impacts by delaying ICSI on the subsequent treatment outcomes (Pujol et al 2018), while others reported no evidence of adverse effects caused by different ICSI timings (Vandenberghe et al 2021). Therefore, we aimed to explore a “safety time window” for ICSI procedures to enable flexibility in workflow arrangement without compromising pregnancy outcomes. Study design, size, duration A systematic review and meta-analysis were performed according to PRISMA guidelines, with protocol registered with PROSPERO (ID: CRD42022296838). The studies were searched for in PubMed, MEDLINE, EMBASE and the Cochrane Library on 16 December 2021, using (“subfertile” OR “sub-fertile” OR “infert*” OR “fertility treatment” OR “women” OR “female” OR “couple”) AND (“ICSI” OR “intracytoplasmic sperm injection” OR “intra-cytoplasmic sperm injection”) AND (“timing” OR “time interval”) AND (“pregnancy” OR “fertili*” OR “birth”) NOT (Review [Publication Type]). Participants/materials, setting, methods Two independent reviewers systematically evaluated each study on patient, intervention, comparison, and outcome (PICO). The Newcastle-Ottawa scale was used for risk of bias assessment in non-randomised trials and observational studies. Further screening was performed separately by the two independent reviewers, with differences mediated by the third reviewer. Data extraction was performed according to Cochrane methods. Clinical pregnancy or live birth data were synthesised from eligible studies depending on availability of raw data in corresponding subgroups. Main results and the role of chance A total of 605 records were hit in the search. After initial exclusion according to PICO, 30 articles were included for further screening for eligibility. For meta-analysis, 4 retrospective cohort studies were eventually included for clinical pregnancy rate assessment while 2 for live birth rate analysis. Due to different groupings in ICSI timing amongst these studies, a series of comparisons on ICSI timings with a cut-off at an hourly increment were set up to pool data from the 4 included studies where applicable. Clinical pregnancy rates were comparable when ICSI was performed (a) 2+ hours (n = 6448, Relative Risk or RR = 1.031, 95% CI 0.964-1.102) in reference to &amp;lt; 2 hours POR (n = 2336), (b) 3+ hours (n = 5101, RR = 1.005, 95% CI 0.945-1.069) in reference to &amp;lt; 3 hours POR (n = 3465), and (c) 4+ hours (n = 3192, RR = 1.017, 95% CI 0.956-1.082) in reference to &amp;lt; 4 hours POR (n = 5374). However, clinical pregnancy rates were significantly compromised when ICSI was performed at 5+ hours (n = 2335, RR = 1.103, 95% CI 1.036-1.175) in reference to &amp;lt; 5 hours POR (n = 7169). Similarly, live birth rate was also significantly reduced when ICSI was performed 5+ hours (n = 2335, RR = 1.155, 95% CI 1.070-1.246) in reference to &amp;lt; 5 hours POR (n = 7169). Limitations, reasons for caution All studies included for meta-analysis were retrospective with heterogeneity. There were various groupings amongst studies due to the wide range of ICSI timings POR, which limits data pooling and subsequent comparisons. A future well designed randomised controlled trial is warranted for further analysis based on better quality evidence. Wider implications of the findings Our results indicate 5 hours POR should be considered the maximum time limit to perform ICSI. This finding, supported by statistics with improved power through meta-analysis, offers valuable guidance to busy clinics. This information could both improve pregnancy outcomes and allow better workflow arrangements without compromising them. Trial registration number not applicable

Does the HCG trigger dose used for IVF impact luteal progesterone concentrations? a randomized controlled trial

Research questionIs there an association between the ovulation trigger dose of human chorionic gonadotrophin (HCG) and endogenous progesterone production during the luteal phase? DesignThis randomized controlled four-arm study, at the Fertility Clinic, Odense University Hospital, Denmark, included women undergoing gonadotrophin-releasing hormone (GnRH) antagonist IVF treatment with ≤11 follicles ≥12 mm. Group 1–3 were triggered with 5000 IU, 6500 IU or 10,000 IU HCG, respectively, receiving 17α-hydroxyprogesterone caproate intramuscularly for luteal-phase support (LPS) to measure endogenous progesterone production. Group 4 received 6500 IU HCG trigger and vaginal progesterone. During the study, the 5000 IU and 10,000 IU HCG groups were switched from urinary to recombinant HCG, as urinary HCG was removed from market. Eight blood samples were drawn during the luteal phase. ResultsNinety-four participants completed the study. There was a significant positive association between the HCG trigger dose and the progesterone at 8 days (P < 0.001), 10 days (P < 0.001) and 14 days (P < 0.001) post-oocyte retrieval. Comparing the groups individually revealed a significant difference in progesterone concentration between low and high trigger doses at 4 days (P = 0.037) and 8 days (P = 0.007) post-oocyte retrieval and between all intervention groups at oocyte retrieval + 6 days: group 1 and 2 (P = 0.011), group 2 and 3 (P = 0.042) and group 1 and 3 (P < 0.001). Higher HCG trigger dose increased the progesterone from the individual follicle. ConclusionsIncreasing HCG trigger doses significantly increased endogenous progesterone concentration during the mid–late luteal phase.

Early Rise of Serum hCG in Gestational Diabetes Mellitus Women With Live Birth Through In Vitro Fertilization Procedure.

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy. The characteristics of early human chorionic gonadotropin (hCG) levels and the rise pattern in patients with GDM after in vitro fertilization (IVF) are unclear. The present investigation was a retrospective cohort analysis of eligible viable pregnancies achieved through IVF in the authors’ hospital between October 2015 and June 2020. The characteristics of initial hCG concentration and the rise pattern in patients with GDM after IVF, and the difference between those of normoglycemic pregnant women, were explored. Using random-effects models, the preferred pattern to describe the increase in log hCG was a quadratic. When gestational age was within 39 days, the linear model adequately characterized the profile, and the average slope was 0.173, yielding a predicted increase of 1.55 (55%) in 1 day and 3.11 (211%) in 2 days. Absolute hCG values—but not the rate of rise—were significantly higher in double embryo transfers and twin pregnancies. Curves reflecting hCG rise from the GDM and non-GDM groups did not differ substantially. The proportion of patients with low initial hCG values (16 days post-oocyte retrieval <100 mIU/ml) was higher in the GDM group (5% vs. 2.09%), although the difference was not statistically significant. Early hCG rise in pregnant women after IVF—whether GDM or non-GDM—could be characterized by quadratic and linear models. However, hCG values on days 14 and 16 post-oocyte retrieval in the GDM group were lower than those in the non-GDM group, with the exception of twin pregnancies. Low hCG values in early pregnancy may be a clue to help predict GDM in the subsequent gestation period.

Prior iodine exposure and impact on thyroid function during controlled ovarian hyperstimulation: A prospective study.

Iodine supplements are recommended for women planning pregnancy, but their impact on thyroid function during controlled ovarian hyperstimulation (COH) and into pregnancy is unknown. The aim of this study was to assess the impact of iodine supplementation on thyroid function during COH. One-hundred and six euthyroid women (thyroid stimulating hormone (TSH) 0.4-2.5mIU/L) planning their first COH cycle were subdivided according to iodine supplementation (nil, <6months, ≥6months) and compared to levothyroxine (LT4)-treated controls. Serial TSH, free thyroxine, free triiodothyronine and thyroglobulin (Tg) levels were recorded at four time points: (i) baseline, (ii) day 7 ovarian stimulation, (iii) ovulation trigger and (iv) two weeks post oocyte retrieval. Oocyte numbers, fertilisation rates and pregnancy outcome were recorded. TSH increased during COH for those women taking iodine supplements for ≥6months (P=0.025). One quarter recorded a TSH level >2.5mIU/L before embryo transfer. A similar increase in TSH was demonstrated by LT4-dependent controls (P=0.024) but not the remaining subgroups. Tg levels did not change during COH in any group but decreased significantly post oocyte retrieval if nil iodine (P<0.0001) or supplemented for ≥6months (P<0.005). Iodine supplementation did not influence oocyte count, fertilisation or implantation rates. Women taking iodine for <6months were four times more likely to achieve a live birth than women taking iodine for longer. Women taking iodine supplements for ≥6months are less able to adapt to the thyroidal demands of COH, with responses comparable to LT4-dependent patients.

Overview of hospitalizations in women undergoing oocyte retrieval for ART in the French national health data system.

What is the incidence rate of complications in women undergoing ART procedures compared to the period prior to their first oocyte retrieval? The study shows a significant increase in the post-ART incidence rate of some complications but a low overall rate of occurrence relative to the total number of oocyte retrievals. ART, widely used in Europe, accounts for 3.3% of births in France. The various studies of ART complications are fairly reassuring, showing relatively low overall complication rates but only few studies have used exhaustive national registers. The cohort for this study was identified from the comprehensive French national hospital-discharge database and includes women under 50 years with a first oocyte retrieval (T0) in 2012-2017, classified in three population subgroups according to the indication for oocyte retrieval: infertility (IF), oocyte donation (OD), and fertility preservation (FP). This study includes 156 916 women whose first oocyte retrieval occurred in 2012-2017 and 542 775 hospitalizations in 2010-2019 (excluding first retrieval). Hospitalizations for complications or others events (oocyte retrieval, delivery, pregnancy loss, and death in the hospital) during the 2 years before (control period) and after their first oocyte retrieval (post-oocyte retrieval period) were compared and expressed per 10 000 person-months (pm). In the IF subgroup, incidence rates were significantly higher after (vs before) retrieval for hospitalized ovarian hyperstimulation syndrome (OHSS) (162 vs 6/10 000 pm), adnexal torsion (14 vs 3), venous thrombosis (8 vs 1), arterial thrombosis (3 vs 1), trauma (2 vs 1), and significantly lower for infections (61 vs 87). The higher incidences of OHSS, adnexal torsion and venous thrombosis could only partially be explained by the occurrence of pregnancy.In the FP subgroup, incidence increased significantly after (vs before) retrieval for hospitalized OHSS (55 vs 0), venous thrombosis (59 vs 4), and infections (176 vs 56). For the OD subgroup, hospitalized OHSS (116 vs 0) and bleeding (24 vs 0) were significantly higher after (vs before) retrieval. The French national health data system, despite all its advantages, present some limitations such as the risk of coding errors. The unavailability of some personal information and the absence of consideration of risk factors prevented us from adjusting the risk. Finally, only complications resulting in hospitalization were analyzed which probably leads to their underestimation. The use of medico-administrative bases will be a valuable tool in public health and will furnish a better overview of the complications. Further studies are needed to complete this analysis. Adding information on drugs would help to better define T0 and less severe complications. N/A. N/A.

What is the optimal timing of intracytoplasmic sperm injection (ICSI) after EGG retrieval? A randomized controlled trial.

To determine if oocyte denudation and ICSI at 36.5 versus 39 h post HCG and/or Lupron trigger (2.5 h versus 5 h post-oocyte retrieval) influences fertilization and blastulation rates in good prognosis couples METHODS: We performed a prospective, randomized controlled trial of 12 patients undergoing IVF with ICSI at an academic fertility center, resulting in 206 MII oocytes analyzed. At time of retrieval, patients with more than 10 oocytes retrieved had their oocytes randomized into two groups-one group for oocyte denudation and ICSI at 36.5 h post HCG and/or Lupron trigger and the other group for these procedures at 39 h post HCG and/or Lupron trigger (2.5 and 5 h after oocyte retrieval). Primary outcomes were fertilization and blastulation rates. No difference was observed in fertilization rate, total blastulation rate, or day of blastulation based on timing of denudation and ICSI (all p > 0.05). Multiple regression analyses for fertilization and blastulation controlling for age and BMI revealed no difference in fertilization based on time of ICSI (p = 0.38, 0.71, respectively). A conditional logistic regression to account for multiple oocytes derived from each patient also found no difference in fertilization or blastulation based on timing of ICSI, even when controlling for age and BMI (p = 0.47, 0.59, respectively). In good prognosis couples, we observed no difference in fertilization or blastulation rates based on timing of ICSI within the currently accepted 2- to 6-h window post-retrieval based on a 34-h trigger. The oocyte appears to have a physiological tolerance for fertilization during this window of time, and variability in the timing of ICSI during this window is unlikely to have an impact on cycle outcome.

WHAT IS THE OPTIMAL TIMING OF INTRACYTOPLASMIC SPERM INJECTION (ICSI) AFTER EGG RETRIEVAL? A RANDOMIZED CONTROLLED TRIAL

To determine if oocyte denudation and ICSI at 36.5 versus 39 h post HCG and/or Lupron trigger (2.5 h versus 5 h post-oocyte retrieval) influences fertilization and blastulation rates in good prognosis couples We performed a prospective, randomized controlled trial of 12 patients undergoing IVF with ICSI at an academic fertility center, resulting in 206 MII oocytes analyzed. At time of retrieval, patients with more than 10 oocytes retrieved had their oocytes randomized into two groups—one group for oocyte denudation and ICSI at 36.5 h post HCG and/or Lupron trigger and the other group for these procedures at 39 h post HCG and/or Lupron trigger (2.5 and 5 h after oocyte retrieval). Primary outcomes were fertilization and blastulation rates. No difference was observed in fertilization rate, total blastulation rate, or day of blastulation based on timing of denudation and ICSI (all p > 0.05). Multiple regression analyses for fertilization and blastulation controlling for age and BMI revealed no difference in fertilization based on time of ICSI (p = 0.38, 0.71, respectively). A conditional logistic regression to account for multiple oocytes derived from each patient also found no difference in fertilization or blastulation based on timing of ICSI, even when controlling for age and BMI (p = 0.47, 0.59, respectively). In good prognosis couples, we observed no difference in fertilization or blastulation rates based on timing of ICSI within the currently accepted 2- to 6-h window post-retrieval based on a 34-h trigger. The oocyte appears to have a physiological tolerance for fertilization during this window of time, and variability in the timing of ICSI during this window is unlikely to have an impact on cycle outcome.

A decision-making algorithm for performing or cancelling embryo transfer in patients at high risk for ovarian hyperstimulation syndrome after triggering final oocyte maturation with hCG.

STUDY QUESTIONCan the grade of ascites, haematocrit (Ht), white blood cell (WBC) count and maximal ovarian diameter (MOD) measured on Day 3 be used to construct a decision-making algorithm for performing or cancelling embryo transfer in patients at high risk for severe ovarian hyperstimulation syndrome (OHSS) after an hCG trigger?SUMMARY ANSWERUsing cut-offs of ascites grade>2, Ht>39.2%, WBC>12 900/mm3 and MOD>85 mm on Day 3, a decision-making algorithm was constructed that could predict subsequent development of severe OHSS on Day 5 with an AUC of 0.93, a sensitivity of 88.5% and a specificity of 84.2% in high-risk patients triggered with hCG.WHAT IS KNOWN ALREADYDespite the increasing popularity of GnRH agonist trigger for final oocyte maturation as a way to prevent OHSS, ≥75% of IVF cycles still involve an hCG trigger. Numerous risk factors and predictive models of OHSS have been proposed, but the measurement of these early predictors is restricted either prior to or during the controlled ovarian stimulation. In high-risk patients triggered with hCG, the identification of luteal-phase predictors assessed post-oocyte retrieval, which reflect the pathophysiological changes leading to severe early OHSS, is currently lacking.STUDY DESIGN, SIZE, DURATIONA retrospective study of 321 patients at high risk for severe OHSS following hCG triggering of final oocyte maturation. High risk for OHSS was defined as the presence of at least 19 follicles ≥11 mm on the day of triggering of final oocyte maturation.PARTICIPANTS/MATERIALS, SETTING, METHODSThe study includes IVF/ICSI patients at high risk for developing severe OHSS, who administered hCG to trigger final oocyte maturation. Ascites grade, MOD, Ht and WBC were assessed in the luteal phase starting from the day of oocyte retrieval. Outcome measures were the optimal thresholds of ascites grade, MOD, Ht and WBC measured on Day 3 post-oocyte retrieval to predict subsequent severe OHSS development on Day 5. These criteria were used to construct a decision-making algorithm for embryo transfer, based on the estimated probability of severe OHSS development on Day 5.MAIN RESULTS AND THE ROLE OF CHANCEThe optimal Day 3 cutoffs for severe OHSS prediction on Day 5 were ascites grade>2, Ht>39.2%, WBC>12 900/mm3 and MOD>85 mm. The probability of severe OHSS with no criteria fulfilled on Day 3 is 0% (95% CI: 0–5.5); with one criterion, 0.8% (95% CI: 0.15–4.6); with two criteria, 13.3% (95% CI: 7.4–22.8); with three criteria, 37.2% (95% CI: 24.4–52.1); and with four criteria, 88.9% (95% CI, 67.2–98.1). The predictive model of severe OHSS had an AUC of 0.93 with a sensitivity of 88.5% and a specificity of 84.2%.LIMITATIONS, REASONS FOR CAUTIONThis is a retrospective study, and therefore, it cannot be excluded that non-apparent sources of bias might be present. In addition, we acknowledge the lack of external validation of our model. We have created a web-based calculator (http://ohsspredict.org), for wider access and usage of our tool. By inserting the values of ascites grade, MOD, Ht and WBC of high-risk patients on Day 3 after oocyte retrieval, the clinician instantly receives the predicted probability of severe OHSS development on Day 5.WIDER IMPLICATIONS OF THE FINDINGSThe present study describes a novel decision-making algorithm for embryo transfer based on ascites, Ht, WBC and MOD measurements on Day 3. The algorithm may be useful for the management of high-risk patients triggered with hCG and for helping the clinician’s decision to proceed with, or to cancel, embryo transfer. It must be emphasized that the availability of the present decision-making algorithm should in no way encourage the use of hCG trigger in patients at high risk for OHSS. In these patients, the recommended approach is the use of GnRH antagonist protocols, GnRH agonist trigger and elective embryo cryopreservation. In addition, in patients triggered with hCG, freezing all embryos and luteal-phase GnRH antagonist administration should be considered for the outpatient management of severe early OHSS and prevention of late OHSS.STUDY FUNDING/COMPETING INTEREST(S)NHMRC Early Career Fellowship (GNT1147154) to C.A.V. No conflict of interest to declare.TRIAL REGISTRATION NUMBERN/A.

The effect of luteal GnRH antagonist on moderate and severe early ovarian hyperstimulation syndrome during in vitro fertilization treatment: a prospective cohort study.

Ovarian hyperstimulation syndrome (OHSS) is a serious complication of assisted reproductive technology (ART) treatment. However, there are limited data regarding the ability of the luteal GnRH antagonist cetrorelix to reduce the incidence of moderate and severe OHSS, and the mechanism remains unclear. Thus, we designed a study to assess the effectiveness of cetrorelix to prevent early moderate and severe OHSS in high-risk patients undergoing controlled ovarian stimulation for IVF/ICSI. In this prospective cohort study, 105 patients with high-risk OHSS undergoing cryopreservation of all embryos were divided into two groups according to their personal choice. The cetrorelix group (n = 65) received 0.25mg of cetrorelix by subcutaneous injection daily, from days 3 to 5 post-oocyte retrieval (POR); the control group (n = 40) received no drug. The primary outcome measures were the incidence and severity of early moderate and severe OHSS. Secondary measures included serum estradiol levels, ovarian volume, ascites volume, hematocrit values, and WBC count on days 3, 6, and 9 POR. VEGF and EGR-1 levels were assessed, and binary logistic regression analysis was applied to predict associations between clinical variables and OHSS. Ninety-six patients were examined. The incidence of moderate and severe OHSS was significantly lower in the cetrorelix group than in the control group (18.03% and 37.14%, respectively; P = 0.037). Serum estradiol (P = 0.013), white blood cell count (P = 0.031), ascites volume (P = 0.036), EGR-1 (P = 0.025), and VEGF levels (P = 0.015) were significantly higher in the control group on day 6 POR than on day 3 POR, while no increase was observed between day 3 POR and day 6 POR in the cetrorelix group, indicating a faster regression of OHSS symptoms. Cetrorelix intervention was associated with the incidence and severity of OHSS (OR 0.29, 95% CI 0.11-0.78, P = 0.014). Cetrorelix effectively reduces the incidence of early moderate and severe OHSS in high-risk women and decreases serum VEGF levels.

Luteal Coasting and Individualization of Human Chorionic Gonadotropin Dose after Gonadotropin-Releasing Hormone Agonist Triggering for Final Oocyte Maturation-A Retrospective Proof-of-Concept Study.

Ovarian stimulation in a gonadotropin-releasing hormone (GnRH) antagonist protocol with the use of GnRH agonist for final oocyte maturation is the state-of-the-art treatment in patients with an expected or known high response to avoid or at least reduce significantly the risk for development of ovarian hyperstimulation syndrome (OHSS). Due to a shortened LH surge after administration of GnRH agonist in most patients, the luteal phase will be characterized by luteolysis and luteal phase insufficiency. Maintaining a sufficient luteal phase is crucial for achievement of a pregnancy; however, the optimal approach is still under debate. Administration of human chorionic gonadotropin (hCG) within 72 h rescues the corpora lutea function; however, the so far often used 1,500 IU still bear the risk for development of OHSS. The recently introduced concept of “luteal coasting” individualizes the luteal phase support by monitoring the progesterone concentrations and administering a rescue dosage of hCG when progesterone concentrations drop significantly. This retrospective proof-of-concept study explored the correlation between hCG dosages ranging from 375 up to 1,500 IU and the progesterone levels in the early and mid-luteal phases as well as the likelihood of pregnancy, both early and ongoing. The chance of pregnancy is highest with progesterone level ≥13 ng/ml at 48 h postoocyte retrieval. Among the small sample size of 52 women studied, it appears that appropriate progesterone levels can be achieved with hCG dosages as low as 375 IU. This may well optimize the chance of pregnancy while reducing the risk of OHSS associated with higher doses of hCG supplementation in the luteal phase.

Ultrasound and hematological changes during early luteal phase in women at high risk for developing ovarian hyperstimulation syndrome.

To assess ultrasound and hematological changes during the early luteal phase following triggering of final oocyte maturation with human chorionic gonadotropin (hCG) in women at high risk for developing ovarian hyperstimulation syndrome (OHSS). This was a retrospective cohort study of 319 women undergoing in-vitro fertilization who were at high risk for OHSS following administration of hCG for the triggering of final oocyte maturation. Patients were treated with a gonadotropin-releasing hormone agonist or antagonist protocol and were monitored for 5 days post-oocyte retrieval (early luteal phase). Severe OHSS was diagnosed in the presence of at least moderate ascites and two or more of the following: maximum ovarian diameter (MOD) > 100 mm, hematocrit (Ht)> 45%, white blood cell count (WBC) >15 000/mm3 , hydrothorax, dyspnea and oliguria. Outcome measures included change in Ht, ascites grade, WBC and MOD, as well as the association between these changes during the early luteal phase. Ascites grade, Ht and WBC increased significantly (P ≤ 0.001) during the early luteal phase, both in patients who developed and in those who did not develop severe early OHSS. MOD increased significantly (P = 0.001) only in patients who developed severe early OHSS. On multivariable analysis, both time following oocyte retrieval and whether severe early OHSS developed were significantly associated with ascites grade, Ht, WBC and MOD; furthermore, there was also a significant interaction between time and development of severe early OHSS for all four variables (P ≤ 0.001). In women at high risk of OHSS, ascites grade, Ht and WBC significantly increased with time over the 5-day observation period, in line with the pathophysiology of the syndrome. Our data support the use of MOD in the diagnosis of severe early OHSS, and provide novel evidence for the role of change in Ht as a patient-specific hemoconcentration marker during development of OHSS. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.