Outcomes of BRCA pre-implantation genetic testing according to the parental mutation origin: a cohort study.

BACKGROUND: The process of gamete formation and early embryonic development involves rapid DNA replication, chromosome segregation and cell division. These processes may be affected by mutations in the BRCA1/2 genes. The aim of this study was to evaluate BRCA mutation inheritance and its effect on early embryonic development according to the parental origin of the mutation. The study question was approached by analyzing in vitro fertilization cycles (IVF) that included pre-implantation testing (PGT-M) for a BRCA gene mutation. METHODS: This retrospective cohort study compared cycles of pre-implantation genetic testing for mutations (PGT-M) between male and female patients diagnosed with BRCA 1/2 mutations (cases), to a control group of two other mutations with dominant inheritance (myotonic dystrophy (MD) and polycystic kidney disease (PKD)). Results were compared according to mutation type and through a generalized linear model analysis. RESULTS: The cohort included 88 PGT-M cycles (47 BRCA and 41 non-BRCA) among 50 patients. Maternal and paternal ages at oocyte retrieval were comparable between groups. When tested per cycle, FSH dose, maximum estradiol level, oocytes retrieved, number of zygotes, and number of embryos available for biopsy and affected embryos, were not significantly different among mutation types. All together 444 embryos were biopsied: the rate of affected embryos was comparable between groups. Among BRCA patients, the proportion of affected embryos was similar between maternal and paternal mutation origin (p = 0.24). In a generalized linear model analysis, the relative oocyte yield in maternal BRCA patients was significantly lower (0.7, as related to the non BRCA group)(p < 0.001). Zygote formation and blastulation were not affected by the BRCA gene among paternal cases (P = 0.176 and P = 0.293 respectively), nor by paternal versus maternal BRCA carriage (P = 0.904 and P = 0.149, respectively). CONCLUSIONS: BRCA PGT-M cycles performed similarly compared to non-BRCA cycles. Inheritance rate and cycle parameters were not affected by the parental origin of the mutation.

How effective is digital educational content in shaping fertility awareness? An interventional, cross-sectional study.

PURPOSE: To determine whether exposure to digital educational content affects fertility awareness and attitudes towards fertility preservation treatments? METHODS: A total of 957 women ages 20 to 45 years participated in this internet-based, interventional, cross-sectional study. A questionnaire assessing knowledge of the reproductive span and attitudes towards fertility preservation treatment was completed by these women before and after exposure to online educational content on ovarian reserve and fertility preservation treatments. Responses before and after exposure to the educational content were compared. RESULTS: Knowledge about female age-related fertility decline improved significantly after exposure to educational content (51.6% vs. 79.6%, p < 0.001). Increased willingness to pursue fertility preservation treatments (38.6% vs. 42.9%, p < 0.001) and to recommend fertility preservation treatments to friends (55% vs. 65.2%, p < 0.001) was observed. Participants who desired to conceive were more positively influenced by the exposure to educational content in their attitudes towards fertility treatments compared to those who do not desire to conceive. CONCLUSIONS: Online educational content has the potential to improve fertility awareness and shape a more positive attitude towards fertility preservation treatments for the public.

Conception after early IVF pregnancy loss: should we wait?

RESEARCH QUESTION: Is the interval length between an early pregnancy loss and the following treatment cycle a predictor for achieving clinical pregnancy among IVF patients? DESIGN: This retrospective cohort study of 257 women who reinitiated treatment after first-trimester IVF pregnancy loss was conducted at a tertiary, university-affiliated medical centre between 1 January 2014 to 1 January 2018. Women aged 18-40 years, with normal uterine cavity, who experienced first-trimester pregnancy loss at less than 14 weeks after IVF, were included. Miscarriages were classified as spontaneous, biochemical, medical or surgical. RESULTS: Among 257 women, interval to subsequent IVF treatment was not associated with achieving pregnancy. Patients after biochemical pregnancy (72.7 ± 56.4, median 60 days) or spontaneous miscarriage (97.7 ± 93.1, median 66 days) had shorter intervals to next cycle, compared with medical (111.9 ± 103.2, median 65 days) or surgical (123.4 ± 111.1, median 84 days) (Kaplan-Meier, P = 0.03) miscarriages. Logistic regression analysis showed that the chance of subsequent pregnancy was affected by the number of embryos transferred (P = 0.009) and the type of miscarriage. Medical (P = 0.005) and surgical (P = 0.017) miscarriages were related to lower likelihood of pregnancy compared with biochemical pregnancy (reference group). When pregnancy was achieved in the first post-miscarriage cycle, the chance of live birth increased with shorter intervals (median 57.5 days), whereas second miscarriage was related to longer intervals (median 82.5 days) between miscarriage and subsequent IVF cycle (P = 0.03). CONCLUSION: On the basis of this cohort, IVF should not be postponed after pregnancy loss, as shorter intervals were associated with greater likelihood of live birth.

Cancer diagnosis among women with recurrent pregnancy loss: a retrospective cohort study.

RESEARCH QUESTION: What is relationship between unexplained recurrent pregnancy loss (RPL) and risk of cancer morbidity? DESIGN: A retrospective observational cohort study was conducted, based on data from a tertiary medical centre. RPL cases (exposed) were defined as women presenting with three or more unexplained confirmed pregnancy losses at 5-24 weeks, whose first visit to the RPL clinic was between 1990 and 2010. The unexposed group included women giving birth who were not RPL patients; these were matched by age and year of giving birth/admission (1:5 ratio). Data from the RPL and the live birth registries were cross-linked to the Israeli national cancer registry according to the unique ID number and merged into one database. RESULTS: The study group comprised 937 RPL patients who were matched by maternal age (P = 1.0) and admission date (P = 0.84) to 4685 women achieving a live birth. There was no difference in overall cancer incidence between groups (adjusted odds ratio [OR] 0.76, 95% confidence interval [CI] 0.55-1.03; P = 0.08). The secondary RPL group showed a trend towards decreased cancer morbidity incidence compared with primary RPL (adjusted OR 0.65, 95% CI 0.41-1.03; P = 0.07). Analysis by cancer type showed a similar risk for breast cancer among women with RPL compared with live birth, but a significantly lower risk for gynaecological cancers among women with RPL (adjusted OR 0.25, 95% CI 0.08-0.79; P = 0.018). CONCLUSIONS: Unexplained RPL may be related to a lower risk of gynaecological cancers, possibly explained by hyper-responsive immunological mechanisms involving uterine natural killer cells.

How far is too far? Does time interval between GnRH antagonist and GnRH agonist trigger in GnRH antagonist cycles matter?

RESEARCH QUESTION: What is a suitable time interval between the last GnRH antagonist exposure and GnRH agonist (GnRHa) triggering for final follicular maturation? DESIGN: A retrospective cohort study including 413 patients undergoing GnRH antagonist cycles in which GnRHa trigger was used, either solely or as a dual trigger. The primary outcome measure was the follicle/mature oocyte ratio. Cycles were analysed according to the time interval between the last GnRH antagonist exposure and the GnRHa triggering: Group 1 included patients with a 12-14 h interval; Group 2: 7-10 h interval; Group 3: 5-6 h interval and Group 4: 2-4 h interval. LH concentration was measured 11-13 h post-GnRHa injection. RESULTS: Median LH value was 65 IU/l. There was a weak but significant correlation between basal LH and the LH surge (R2 = 0.137, P < 0.001). Although square root LH values differed significantly between study groups (P < 0.001; higher in Groups 2 and 3), the follicle/mature oocyte ratio was not different across the four antagonist-agonist interval groups and no correlation was detected between the post-trigger LH concentration and the follicle/oocyte ratio (R2 = 0.011). In a model integrating age, day 3 FSH concentration, maximal oestradiol and body mass index along with the study groups, none of these factors was significantly related to the follicle/mature oocyte outcome ratio. Insufficient surge (LH < 15 IU/l) occurred in 14 (3.4%) cases. Rates of insufficient LH surge did not differ significantly between the groups (2.4%, 3.2%, 3.4% and 7.1% in Groups 1 to 4, respectively; P = 0.5). CONCLUSIONS: LH concentrations post-GnRHa trigger differ in regard to antagonist-agonist intervals, but the follicle/mature oocyte ratio achieved was not affected.

Oral contraceptive pills as an option for non-surgical management of retained products of conception - a preliminary study.

Many Patients with persistent retained products of conception prefers to avoid surgical interventions, such as a dilatation and curettage (D&C) that might pose an additional future risk to their already compromised fertility or obstetric performance. The aim of this study was to the possibility of induced withdrawal bleeding following oral contraceptive administration as a non-surgical treatment for patients with persistent retained products of conception (RPOC). A retrospective study of patients presenting with retained products of conception (RPOC) after failed expectant management or after treatment with PGE1 was performed. Twelve women presenting with RPOC at ≤8 weeks gestation with minimal to mild vaginal bleeding and no signs of infection were treated with oral contraceptive pill (OCP) containing 0.03 mg ethinylestradiol and 0.15 mg of desogestrel for 3 weeks. Out of the 12 patients treated, nine women (75%) successfully expelled the RPOC after completing the three-week course of OCPs. The three cases (25%) that did not resolve following OCP treatment had pregnancy products with positive blood flow on Doppler examination. We conclude that OCPs may be a useful medical treatment option for persisting RPOC in selected patients with absence blood flow on Doppler examination wishing to avoid surgical intervention.

Number of Oocytes Retrieved as a Criterion for "Freeze-All" Strategy versus a Single "Rescue" Bolus of Low-Dose Human Chorionic Gonadotropin Following GnRH Agonist for Ovulation Triggering: A Pilot Study.

AIM: To evaluate the number of oocytes retrieved as a criterion - when to use a "freeze-all" or low-dose "rescue human chorionic gonadotropin (hCG)" strategy. METHODS: A retrospective study. Instead of the classic hCG trigger, an E2 level of ≥3,000 pg/mL was used to trigger ovulation with GnRH agonist. The decision whether to "freeze all" or perform fresh embryo transfer (ET) with a bolus of hCG was made based on a maximum number of 20 oocytes retrieved. Beyond this cut off, a "freeze-all" strategy was implemented. Below this cut-off value, a fresh ET using a single bolus of 62.5 µg hCG on day 3 following oocyte pick-up was performed. The main outcome measures were clinical pregnancy rates and ovarian hyperstimulation syndrome (OHSS). RESULTS: E2 and progesterone levels increased after the rescue hCG bolus administration (E2 from 643.4 ± 311.1 to 1,086.1 ± 574.7 pg/mL, p = 0.003 and progesterone from 13.1 ± 4.8 to 39.2 ± 28.7 ng/mL, p < 0.0001). The clinical pregnancy rates were 25% in the freeze-all group and 32% in the rescue hCG group (p = 0.57). OHSS was not reported in either group. CONCLUSIONS: Both strategies seem to be efficacious and safe. An upper limit of 20 retrieved oocytes appears to be safe for applying a rescue hCG strategy.

Intramuscular versus Vaginal Progesterone Administration in Medicated Frozen Embryo Transfer Cycles: A Randomized Clinical Trial Assessing Sub-Endometrial Contractions.

OBJECTIVE: The study aimed to assess whether sub-endometrial contractility is reduced by the use of intramuscular (IM) progesterone. DESIGN: This is a randomized clinical trial. Patients assigned to a medicated day 5 frozen embryo transfer (FET) were randomly allocated to "vaginal progesterone" or "IM progesterone": patients randomized to the vaginal arm were treated with 200 mg micronized progesterone 3 times daily while patients randomized into the IM progesterone arm were treated with a single daily injection of 50 mg progesterone in oil. The main outcome measure was the number of sub-endometrial contractions (waves) per minute 1 day before a blastocyst embryo transfer. RESULTS: Thirty-four patients were enrolled. The progesterone serum concentration was significantly higher in patients using the IM progesterone (85.2 ± 50.1 vs. 30.3 ± 11.2 nmol/L, respectively) but this did not translate into a lower sub-endometrial contractility (2.4 ± 4.8 vs. 1.4 ± 1.1 contraction/min, respectively). Clinical pregnancy rates were comparable between groups. The number of sub-endometrial waves was significantly lower among pregnant patients (p = 0.02). CONCLUSIONS: The use of IM progesterone in medicated FET cycles does not reduce the sub-endometrial activity compared to vaginal progesterone administration. Our data support a poor clinical pregnancy outcome with high wave activity, regardless of the progesterone mode.

Sub-fertile sperm cells exemplify telomere dysfunction.

PURPOSE: The purpose of this study was to evaluate telomere homeostasis in sub-fertile compared to fertile human sperm. METHODS: This observational, comparative study included 16 sub-fertile men who required intracytoplasmic sperm injection and 10 fertile men. At least 100 sperm cells from each participant were assessed. Main outcome measures were telomere length and telomere aggregates. Telomerase RNA component (TERC) copy number and telomere capture were assessed using fluorescence in situ hybridization technique and human telomerase reverse transcriptase (hTERT) using immunohistochemistry. RESULTS: Clinical backgrounds were similar. The percentage of sperm cells with shorter telomeres was higher among the sub-fertile compared to the fertile participants (3.3 ± 3.1 vs. 0.6 ± 1.2%, respectively; P < 0.005). The percentage of cells with telomere aggregates was significantly higher in the sub-fertile group (15.12 ± 3.73 vs. 4.73 ± 3.73%; P < 0.005). TERC gene copy number was similar between groups. The percentage of cells that were positive for hTERT was lower in the sub-fertile group (3.81 ± 1.27 vs. 8.42 ± 1.80%; P < 0.005). Telomere capture rates were higher among the sub-fertile sperm cells (P < 0.005). CONCLUSIONS: Sub-fertile sperm cells have short telomeres that are elongated by the alternative pathway of telomere capture. Dysfunctional telomeres may affect sperm fertilizability.

What are the prevalence, characteristics and significance of fetal lateral neck cysts detected in an early anatomical scan?

PURPOSE: This study evaluated the association of fetal lateral neck cysts (FLNC) with adverse pregnancy outcomes, in relation to specific sonographic characteristics and co-existing findings. METHODS: Pregnancies in which FLNC were detected by a single examiner in early anatomical scans (14-16 weeks) were included. Data regarding the pregnancy and its outcome were retrieved from telephone-based questionnaires, patient charts and from the examiner's reports. RESULTS: 654 cases of FLNC were detected among 9446 early anatomical scans (6.9%). Complete data regarding 219 pregnancies were available. FLNC were significantly more prevalent in males (65.2%). The prevalence of heart malformations was 3.2% [all were non-isolated cases or with abnormal nuchal translucency (NT) and/or nuchal fold (NF)]. Amniocentesis performed in 165 pregnancies was abnormal in 1.2%. Among 206 children born from this cohort, adverse medical outcomes were reported in 5.3%. The likelihood of adverse pregnancy outcomes was significantly higher in non-isolated cases and in cases with abnormal NT or NF. Sonographic characteristics such as cyst size and bilateral findings were not linked to adverse pregnancy outcomes. CONCLUSION: Isolated FLNC are benign findings which do not require additional work up. FLNC with additional sonographic abnormalities are associated with a significantly increased risk for adverse pregnancy outcomes.

hCG Triggering in ART: An Evolutionary Concept.

Human chorionic gonadotropin (hCG) is no longer a single, omnipotent ovulation triggering option. Gonadotropin releasing hormone (GnRH) agonist, initially presented as a substitute for hCG, has led to a new era of administering GnRH agonist followed by hCG triggering. According to this new concept, GnRH agonist enables successful ovum maturation, while hCG supports the luteal phase and pregnancy until placental shift.

Adhesions at repeat cesarean delivery: is there a personal impact?

PURPOSE: The rise in the rate of cesarean deliveries highlights complications related to adhesion formation. This study evaluated whether the incidence and severity of adhesions secondary to repeat cesarean deliveries are a consequence of repeated surgeries or due to an individual's propensity to develop adhesions. METHODS: A retrospective chart review was conducted for 160 patients who had more than two repeat cesarean deliveries in a single teaching hospital. Data regarding intra-abdominal adhesions were collected. The severity, location, density and amount of adhesions were evaluated based on standard operative reports. Adhesion progression in subsequent cesarean deliveries was evaluated for each individual patient. RESULTS: 69/160 (43 %) patients developed significant adhesions following the primary cesarean delivery. Of these, 46 (67 %) had significant adhesions at the second surgery. Of the 91 (57 %) patients, who did not develop significant adhesions after the primary cesarean delivery, 34 (37 %) had significant adhesions at the third surgery. A patient presenting with significant adhesions at her second cesarean had a 1.88-fold risk for significant adhesions at her third cesarean (95 % CI 1.3-2.7). CONCLUSIONS: Our results suggest that adhesion development might be influenced by individual factors more than by the number of cesarean deliveries.

Pregnancy-associated listeriosis: clinical characteristics and geospatial analysis of a 10-year period in Israel.

BACKGROUND: Listeria monocytogenes is a foodborne pathogen that causes life-threatening infections in elderly, immunocompromised, and pregnant women. In pregnancy it may cause fetal loss or a preterm delivery, and the neonate is prone to neonatal sepsis and death. METHODS: We created a cohort of all L. monocytogenes cases during 10 years (1998-2007) in Israel, by a comprehensive review of cases in hospitals throughout the country and cases reported to the Ministry of Health. RESULTS: One hundred sixty-six pregnancy-related listeriosis cases were identified, resulting in a yearly incidence of 5-25 cases per 100 000 births. Presentation associated with fetal demise was more common in the second trimester (55.3%), and preterm labor (52.3%) and abnormal fetal heart rate monitoring (22.2%) were more common in the third trimester (P = .001). Fetal viability was low in the second trimester (29.2%) and much higher (95.3%) in the third trimester. Each additional week of pregnancy increased the survival chance by 33% (odds ratio, 1.331 [95% confidence interval, 1.189-1.489]). A single case of maternal mortality was identified. Listeria monocytogenes serotype 4b was more common in pregnancy-related than in non-pregnancy-related cases (79.5% vs 61.3%, P = .011). Pulsed-field gel electrophoresis analysis suggested that 1 pulsotype is responsible for 35.7% of the pregnancy cases between 2001 and 2007. This clone is closely related to the Italian gastroenteritis-associated HPB2262 and the invasive US Scott A L. monocytogenes strains. CONCLUSIONS: Our survey emphasizes the high rate of pregnancy-related listeriosis in Israel and shows that specific clones might account for this.

Is severe OHSS associated with adverse pregnancy outcomes? Evidence from a case-control study.

Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially life-threatening complication of fertility treatment. This study evaluated pregnancy outcomes of women hospitalized for severe OHSS. A case-control study was performed of 125 women who were hospitalized due to severe OHSS compared with a control group, consisting of 156 women matched by age and aetiology of infertility, who conceived via IVF and did not develop OHSS. Among women with singleton pregnancies, patients with severe OHSS delivered significantly earlier (37.96 versus 39.11 weeks) and had smaller babies (2854 g versus 3142 g) compared with the matched controls. Similarly, rates of preterm delivery (<34 weeks of gestation: 8.9% versus 0%, P < 0.01; <37 weeks of gestation: 20.5% versus 5.1%, P < 0.01) were significantly increased among patients in the study group. There were no between-group differences in the rates of gestational diabetes, gestational hypertension and intrauterine growth restriction. In contrast, twin pregnancies following OHSS were not significantly different from matched control twins, with regard to the rates of delivery <34 weeks and <37 weeks of gestation, gestational diabetes, gestational hypertension and intrauterine growth restriction. In conclusion, severe OHSS at early gestation is associated with adverse pregnancy outcome only in singleton gestations.

General anesthesia with propofol during oocyte retrieval and in vitro fertilization outcomes: retrospective cohort study.

General anesthesia is frequently administered during oocyte retrieval. Its effects on the outcomes of IVF cycles are uncertain. This study investigated whether administration of general anesthesia (specifically propofol) during oocyte retrieval affects IVF outcomes. A total of 245 women undergoing IVF cycles were included in this retrospective cohort study. IVF outcomes of 129 women who underwent oocyte retrieval under propofol anesthesia and 116 without anesthesia were compared. Data were adjusted for age, BMI, estradiol on triggering day and total gonadotropin dose. The primary outcomes were fertilization, pregnancy and live birth rates. A secondary outcome was the efficiency of follicle retrieval associated with the use of anesthesia. Fertilization rate was lower in retrievals under anesthesia compared to without (53.4% ± 34.8 vs. 63.7% ± 33.6, respectively; p = 0.02). There was no significant difference in the ratio of expected to retrieved oocytes between retrievals with and without anesthesia (0.8 ± 0.4 vs. 0.8 ± 0.8, respectively, p = 0.96). The differences in pregnancy and live birth rates between the groups were not statistically significant. General anesthesia administered during oocyte retrieval may have adverse effects on the fertilization potential of oocytes. This impact on the developmental potential of oocytes may lead to negative IVF outcomes and should be investigated further.

Ovarian reserve in women with cystic fibrosis: is this a cause of sub-fertility?

BACKGROUND: Over the past two decades, increasing number of people with cystic fibrosis (CF) survive into adulthood. Compared to the general population, sub-fertility is an obstacle for many women with CF (wwCF). Decreased ovarian reserve has been proposed as a possible cause, but limited data is available to support this. The aim of this study was to evaluate the ovarian reserve in wwCF and to correlate this with patients' demographic and clinical data. METHODS: Reproductive-aged wwCF were enrolled during their routine medical appointments. Assessment included Anti-Mullerian hormone (AMH) levels, routine blood tests and antral follicular count (AFC) evaluation. Additionally, demographic, and clinical information were collected. RESULTS: A total of wenty-three wwCF were enrolled, with ages ranging from 19 to 40 years (median 27 years). Among the fourteen wwCF who were considering pregnancy, five (35.7%) disclosed undergoing an infertility assessment and receiving fertility treatments. All but one patient had an Anti-Mullerian hormone (AMH) level between the 5th and 95th % for age. Measurement of the antral follicular count (AFC) was possible in 12 of the 23 patients and was ranging 8-40 with a median of 17. The proportion of wwCF presenting below median AMH values was not different in sub-fertile as compared to fertile wwCF (P value 0.54). There were no correlations between AMH levels and disease severity parameters. AMH seemed to be relatively higher in wwCF with mild class mutations, but this was not shown to have statistical significance. CONCLUSIONS: Our results, in contrast with the limited available published data, do not support the hypothesis that decreased ovarian reserve plays a major role in infertility in wwCF.

Point-of-Care Ultrasonography in a Pulmonary Hypertension Clinic: A Randomized Pilot Study.

Pulmonary arterial hypertension (PAH) is a rare condition with the potential to progress to right heart failure. Point-of-Care Ultrasonography (POCUS), used and interpreted in real time at the bedside to further the cardiopulmonary assessment, has the potential to improve the longitudinal care of PAH patients in the ambulatory setting. Patients from PAH clinics at two academic medical centers were randomized to either a POCUS assessment cohort or non-POCUS standard care (ClinicalTrials.gov identifier NCT05332847). The POCUS group received blinded heart, lung, and vascular ultrasound assessments. Thirty-six patients were randomized to the study and followed over time. Mean age was 65 in both groups and majority female (76.5% and 88.9% females in POCUS and control, respectively). Median time for POCUS assessment was 11 min (range 8-16). There were significantly more changes in management in the POCUS group than control (73% vs. 27%, p-value < 0.001). Multivariate analysis revealed that management changes were more likely to occur with a POCUS assessment, with an odds ratio (OR) of 12 when POCUS was added to physical exam vs. OR of 4.6 compared to physical examination alone (p < 0.001). POCUS in the PAH clinic is feasible and, when combined with physical examination, increases the number of findings and results in changes in management without significantly prolonging visit encounters. POCUS may help support clinical evaluation and decision making in ambulatory PAH clinics.

Boosting Dose of Pfizer-BioNtech mRNA Vaccine Against SARS-CoV-2 Does Not Affect Reproductive Outcomes in In-Vitro Fertilization Patients: A Cohort Study.

Background: Since the introduction of anti-COVID-19 mRNA vaccination, few studies have shown that reproductive outcomes in artificial reproductive technology (ART) treatments are not impaired, after receiving the two-dose regimen. Our aim was to investigate whether a boosting dose of the Pfizer-BioNtech mRNA vaccine affects reproductive outcomes in ART patients. Materials and Methods: This is a prospective observational study, including 157 consecutive in-vitro fertilization (IVF) cycles between October 1, 2021, and November 24, 2021, in a single university affiliated IVF unit. We included female patients going through an ART procedure and male partners in cases of utilization of a fresh sperm sample. The study population was divided into four groups according to exposure status: vaccinated and boosted patients (three total doses of Pfizer-BioNtech mRNA vaccine), patients who were vaccinated without the booster dose (one or two vaccine doses), PCR-confirmed convalescent COVID-19 patients, and unvaccinated nonconvalescent patients. Main outcome measure was clinical pregnancy rate. Results: In total, 99 (63%) female patients were vaccinated three times, 24 (15.3%) were vaccinated without the booster dose, 21 (13.4%) were convalescent, and 13 were (8.3%) unexposed. Although age differed between study groups, vaccination exposure status did not affect treatment outcome: clinical pregnancy rates, maximal estradiol levels, and number of oocytes retrieved did not differ significantly between study groups (p = 0.78, 0.50, and 0.97, respectively). Vaccinated patients who received a boosting vaccine dose were treated within 43.3 ± 30.9 days after receiving the last dose, whereas vaccinated, nonboosted, or convalescent patients were treated 168.7 ± 53 and 209.6 ± 85.1 days after their last exposure, respectively. We stratified the male cohort according to boosting vaccine dose status. Sperm concentration and motility did not differ significantly after boosting (p = 0.49 and 0.49, respectively). Conclusions: Our results provide further reassurance that IVF outcomes are not affected by the anti-SARS-CoV-2 Pfizer-BioNtech mRNA vaccine, in particular the three-dose regimen.

Standardization of Post-Vitrification Human Blastocyst Expansion as a Tool for Implantation Prediction.

The increased use of vitrified blastocysts has encouraged the development of various criteria for selecting the embryo most likely to implant. Post-thaw assessment methods and timetables vary among investigators. We investigated the predictive value of well-defined measurements of human blastocyst re-expansion, following a fixed incubation period. Post-thaw measurements were taken exactly at 0 and 120 ± 15 min. Minimum and maximum cross-sectional axes were measured. Three groups were defined: Group 1: embryos that continued to shrink by 10 µm or more; group 2: embryos that ranged from -9 to +9 µm; and group 3: re-expansion of 10 µm or more. Patient and morphokinetic data were collected and integrated into the analysis. A total of 115 cases were included. The clinical pregnancy rate for group 1 was 18.9%; group 2, 27%; and group 3, 51.2% (p = 0.007). Pre-thaw morphologic grading and morphokinetic scores of the study groups did not reveal differences. p-values were 0.17 for the pre-thaw morphologic score, 0.54 for KID3, and 0.37 for KID5. The patients' demographic and clinical data were similar. The clinical pregnancy rate correlated with the degree of thawed blastocyst re-expansion measured 2 h after incubation. This standardized measure is suggested as a tool to predict the potential of treatment success before embryo transfer.

Luteal phase support in fresh and frozen embryo transfers.

Context: Luteal phase support (LPS) has become an essential component of IVF protocols following both fresh and frozen embryo transfers, yet there is still controversy with regards to the optimal protocol of LPS to enhance treatment outcome. Search strategy: A search via PubMed for all the selected topics was limited to publications from the past 10 years and to English language. We subsequently searched the reference lists of retrieved articles. Where available, RCTs were chosen over non-randomized studies. Here we provide an updated review of the current literature on various issues relating to LPS, in both fresh and frozen embryo transfers. The timing of LPS initiation as well as the route of administration and dosing are discussed for both fresh and frozen transfers. A separate discussion for frozen thawed embryo transfer in natural cycles and non-ovulatory cycles is presented. Conclusions: We present data that supports the use of Progesterone LPS in fresh and frozen embryo transfers. No benefits were found to the addition of hCG or estradiol to progesterone LPS in fresh transfers, however GnRH agonist may have a role. IM Progesterone was not advantageous over vaginal progesterone in fresh transfers but was superior in frozen transfers. The timing of LPS introduction, the interval to embryo transfer, as well as the serum concentration of progesterone, have significant effects on the success of the treatment.