High prevalence of low prognosis by the POSEIDON criteria in women undergoing planned oocyte cryopreservation.

OBJECTIVE: Planned oocyte cryopreservation (OC) is being increasingly utilized worldwide. However, some women cannot accumulate sufficient oocytes because of poor response to stimulation. The POSEIDON classification is a novel system to classify patients with 'expected' or 'unexpected' inappropriate ovarian response to exogenous gonadotropins. Our study aimed to examine the prevalence of POSEIDON patients among women undergoing planned OC. STUDY DESIGN: We retrospectively reviewed the first cycles of 160 consecutive patients undergoing planned OC. Patients were classified into the four POSEIDON groups or as 'non-POSEIDON' based on age, AMH level and the number of oocytes retrieved. The primary outcome measure was the prevalence of POSEIDON patients. RESULTS: Overall, 63 patients (39.4 %) were classified as POSEIDON patients, 12 in group 1, 12 in group 2, 8 in group 3, and 31 in group 4. Compared to non-POSEIDON patients, POSEIDON patients had increased basal FSH levels and reduced serum AMH levels and antral follicle counts, required higher FSH starting doses and increased gonadotropin requirements and reached lower peak serum estradiol levels. Additionally, POSEIDON patients had a lower number of oocytes retrieved (7.6 ± 3.1 vs.20.2 ± 9.9, p < 0.001) and vitrified (5.8 ± 2.9 vs.14.7 ± 6.8, p < 0.001) than non-POSEIDON counterparts, respectively. CONCLUSION: We found a high prevalence of patients being classified as low prognosis according to the POSEIDON criteria among patients seeking planned OC. POSEIDON patients had increased gonadotropin requirements and a significantly lower number of oocytes retrieved and vitrified. This novel, unexpected finding adds clinically relevant information for counselling and management of patients undergoing planned OC.

Obstetric and Perinatal Outcomes following Ovulation Induction and Unassisted Pregnancies in the Same Mother.

OBJECTIVE: We aimed to assess whether ovulation induction treatments affect obstetric and neonatal outcomes. STUDY DESIGN: This was a historic cohort study of deliveries in a single university-affiliated medical center between November 2008 and January 2020. We included women who had one pregnancy following ovulation induction and one unassisted pregnancy. The obstetric and perinatal outcomes were compared between pregnancies following ovulation induction and unassisted pregnancies, so that each woman served as her own control. The primary outcome measure was birth weight. RESULTS: A total of 193 deliveries following ovulation induction and 193 deliveries after unassisted conception by the same women were compared. Ovulation induction pregnancies were characterized by a significantly younger maternal age and a higher rate of nulliparity (62.7 vs. 8.3%, p < 0.001). In pregnancies achieved by ovulation induction, we found a higher rate of preterm birth (8.3 vs. 4.1%, p = 0.02) and instrumental deliveries (8.8 vs. 2.1%, p = 0.005), while cesarean delivery rates were higher following unassisted pregnancies. Birth weight was significantly lower in ovulation induction pregnancies (3,167 ± 436 vs. 3,251 ± 460 g, p = 0.009), although the rate of small for gestational age neonates was similar between the groups. On multivariate analysis, birth weight remained significantly associated with ovulation induction after adjustment for confounders, while preterm birth did not. CONCLUSION: Pregnancies following ovulation induction treatments are associated with lower birth weight. This may be related to an altered placentation process following uterine exposure to supraphysiological hormonal levels. KEY POINTS: · Ovulation induction entails lower birthweight.. · This may relate to supraphysiological hormonal levels.. · Monitoring fetal growth is advised in such cases..

The effect of SARS-CoV-2 mRNA vaccination on AMH concentrations in infertile women.

RESEARCH QUESTION: Does SARS-CoV-2 mRNA vaccination affect the ovarian reserve of infertile women undergoing IVF? DESIGN: This was a prospective observational study at a single university-affiliated IVF unit that included infertile women aged 18-44 years who were undergoing IVF/intracytoplasmic sperm injection between November 2020 and September 2021, had received two doses of SARS-CoV-2 mRNA vaccination and had undergone measurement of baseline anti-Müllerian hormone (AMH) concentration within the 12 months preceding their recruitment. AMH concentrations before and after vaccination were evaluated and compared. RESULTS: Overall, 31 women were included in the study. The median AMH concentrations before and after COVID-19 vaccine were comparable (1.7 versus 1.6 g/ml, respectively, P = 0.96). No correlation was found between the participant's anti-COVID-19 antibody titre and the change in AMH concentration. CONCLUSIONS: SARS-CoV-2 mRNA vaccination does not adversely affect ovarian reserve, as shown by comparing serum AMH concentrations before and after vaccination. These findings may serve as a counselling tool for clinicians to reassure women undergoing fertility treatment that SARS-CoV-2 mRNA vaccination is safe.

Prediction, assessment, and management of suboptimal GnRH agonist trigger: a systematic review.

PURPOSE: This systematic review aimed to identify baseline patient demographic and controlled ovarian stimulation characteristics associated with a suboptimal response to GnRHa triggering, and available options for prevention and management of suboptimal response. METHODS: PubMed, Google Scholar, Medline, and the Cochrane Library were searched for keywords related to GnRHa triggering, and peer-reviewed articles from January 2000 to September 2021 included. RESULTS: Thirty-seven studies were included in the review. A suboptimal response to GnRHa triggering was more likely following long-term or recent oral contraceptive use and with a low or high body mass index. Low basal serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol serum levels were correlated with suboptimal oocyte yield, as was a low serum LH level on the day of triggering. A prolonged stimulation period and increased gonadotropin requirements were correlated with suboptimal response to triggering. Post-trigger LH < 15 IU/L best correlated with an increased risk for empty follicle syndrome and a lower oocyte retrieval rate. Retriggering with hCG may be considered in patients with suboptimal response according to post-trigger LH, as in cases of failed aspiration. CONCLUSION: Pre-treatment assessment of patient characteristics, with pre- and post-triggering assessment of clinical and endocrine cycle characteristics, may identify cases at risk for suboptimal response to GnRHa triggering and optimize its utilization.

Can endocrine characteristics of early pregnancy following natural cycle cryopreserved embryo transfer predict live birth?

RESEARCH QUESTION: Can serial measurements of serum oestradiol, progesterone and ß-human chorionic gonadotrophin (HCG) concentrations, starting from the day of the first positive pregnancy test, predict live birth after natural cycle frozen-thawed embryo transfer (NC-FET)? DESIGN: This was a historical cohort study of women with a positive pregnancy test following NC-FET, between March 2009 and January 2020. Serum ß-HCG, oestradiol and progesterone concentrations were measured on the day of the first pregnancy test and 48 and 96 h later. Pregnancies resulting in a live birth were compared with non-viable pregnancies. RESULTS: Of 101 women with a positive pregnancy test included in the study, 78 had a live birth and 23 had a non-viable pregnancy. Serum ß-HCG concentrations were comparable on the day of the first pregnancy test (P = 0.09) but became significantly higher in women with a live birth 48 and 96 h later (P = 0.018 and P = 0.003). Serum oestradiol concentrations were higher in women with a live birth at all three measurements (P = 0.02, P = 0.007 and P = 0.02). Serum progesterone concentrations were higher 48 h after the first pregnancy test in women with a live birth (P = 0.04). On multivariate analysis, after controlling for the women's ages and number of embryos transferred, serum concentrations above the 25th percentile for oestradiol (>488-526 pmol/L) and progesterone (>63-70 nmol/L) were independent predictors of live birth at all three measurements. CONCLUSIONS: Increased serum oestradiol and progesterone concentrations in early NC-FET pregnancies are associated with increased likelihood of live birth. Oestradiol and progesterone concentrations can be used in conjunction with ß-HCG to predict pregnancy viability and assist in patient counselling.

Should women receive luteal support following natural cycle frozen embryo transfer? A systematic review and meta-analysis.

BACKGROUND: Spontaneous ovulation during a natural menstrual cycle is frequently used for timing frozen embryo transfer (FET). Nevertheless, it remains unclear whether or not women should receive luteal phase support (LPS) following natural cycle frozen embryo transfer (NC-FET). OBJECTIVE AND RATIONALE: The aim of this systematic review and meta-analysis was to study whether the administration of LPS improves the reproductive outcome following NC-FET. SEARCH METHODS: We conducted a systematic search of the literature published in Medline/PubMed, Embase and the Cochrane Library, from January 2000 until December 2020. We included all original English, peer-reviewed articles, irrespective of the study design. The search strategy included keywords related to NC-FET and luteal phase support. Studies reporting the results of artificial or stimulated FET cycles were excluded. OUTCOMES: Our systematic search generated 416 records. After screening, eight studies were included in the review and seven studies were included in the meta-analysis. Two studies (n = 858) used hCG and six studies (n = 1507) used progesterone for luteal support. Four studies were randomised controlled trials (RCTs), whereas the other four were historic cohort studies. In a meta-analysis using a random effects model, hCG administration for LPS did not increase the clinical pregnancy rate (CPR) (two studies, odds ratio (OR) 0.85, 95% CI 0.64-1.14). On the other hand, progesterone LPS was associated with a higher CPR (five studies, OR 1.48, 95% CI 1.14-1.94), and a higher live birth rate (LBR) (three studies, OR 1.67, 95% CI 1.19-2.36). The association between progesterone LPS and the LBR remained significant after excluding non-randomised studies. WIDER IMPLICATIONS: The available evidence indicates that progesterone administration for LPS is beneficial following NC-FET. There is no evidence to support the administration of hCG for LPS in these cases. Additional large RCTs are necessary to improve the quality of evidence and validate our findings.

Future fertility of patients with zero oocytes yield in their first IVF cycle attempt.

PURPOSE: We aim to estimate the future fertility of patient undergoing their first IVF cycle attempt with no oocyte retrieved, and to identify factors that might predict those who will conceive in subsequent IVF cycle attempt. METHODS: A cohort retrospective study of all consecutive women attending our IVF unit, for their first IVF cycle attempt, between January 2013 to December 2019, who reached the ovum pick-up (OPU) stage with zero oocyte retrieved. Patients' characteristics and infertility-treatment-related variables in the first IVF cycle attempt were compared between those who conceived in a subsequent cycle and those who did not. Moreover, infertility-treatment-related variables during successful cycles resulting in pregnancy were compared to those without. RESULTS: 59 met the study inclusion criteria, yielding zero oocytes. During the follow-up period, 12 (20.3%) women conceived (one conceived twice), and 8 (14%) gave birth to a live infant. Cumulative live-birth rate per OPU and per patients were 4% and 14%, respectively. Clinical pregnancies were achieved after 3.61+1.4 cycle attempts (range: 1-6), with no live-births following the fifth IVF cycle attempt. No in-between group differences were observed in ovarian stimulation variables of their first IVF cycle attempt. Moreover, in those cycles resulting in pregnancy, patients achieved a significantly higher number of fertilized oocytes (2.15+1.5 vs 0.94+1.5, respectively; p<0.01) and a higher mean top-quality embryos (TQE) (1.76+0.9 vs 0.73+1.2, respectively; p<0.003). CONCLUSION: Women yielding zero oocytes at their first IVF cycle attempt, may achieve 14% cumulative live-birth rate after 5 IVF cycle attempts. Moreover, those who conceived in subsequent IVF cycle attempts were those achieving 2 or more fertilized oocytes/TQE.

A randomized controlled trial of vaginal progesterone for luteal phase support in modified natural cycle - frozen embryo transfer.

OBJECTIVE: Our aim was to study whether luteal phase support (LPS) increases the live-birth rate (LBR) in women undergoing modified natural cycle (mNC) frozen-thawed embryo transfer (FET). METHODS: In a randomized controlled trial, conducted at a university-affiliated tertiary medical center, a total of 59 patients aged 18-45 years, underwent mNC-FET. FET was performed in mNC following ovulation triggering by hCG. Patients were randomized into two groups; The No-LPS Group included 28 women who did not receive LPS, and the LPS Group included 31 women who received vaginal progesterone for LPS. The main outcome measure was LBR. RESULTS: Baseline demographic and clinical characteristics were comparable between the study groups. The no-LPS group and the LPS group did not differ with regard to clinical pregnancy rate (21.4% vs. 32.3%; respectively, p = .35), LBR (17.9% vs. 19.4%; respectively, p = .88), or spontaneous miscarriage rate (3.6% vs. 12.9%; respectively, p = .35). On multivariate logistic regression analysis, LPS was not associated with LBR after controlling for confounders. CONCLUSION: The results of our study suggest that LPS after mNC-FET does not improve the reproductive outcome, and therefore, might not be necessary.C linicaltrials.gov identifier: NCT01483365.

Does the interval between the last GnRH antagonist dose and the GnRH agonist trigger affect oocyte recovery and maturation rates?

RESEARCH QUESTION: Does the time interval between the last gonadotrophin-releasing hormone (GnRH) antagonist dose and the GnRH agonist trigger affect the efficacy of the trigger in IVF treatments? DESIGN: This retrospective cohort study involved 53 normogonadotrophic patients undergoing GnRH antagonist-based IVF cycles, in a single academic centre between June 2019 and February 2020, in whom a GnRH agonist was used for final ovulation triggering. RESULTS: The mean time interval between the last GnRH antagonist dose and GnRH agonist triggering was 4.6 ± 2.7 h (range 1-12 h). There was no correlation between the antagonist-agonist interval and the oocyte recovery rate (Spearman's correlation coefficient [CC] 0.02, P = 0.89) or metaphase II oocyte rate (CC 0.006, P = 0.96). On multivariate analysis, the antagonist-agonist interval was not associated with treatment outcomes, after adjusting for the women's age and body mass index. CONCLUSIONS: This is the first study assessing the efficacy of the GnRH agonist trigger in relation to the time interval between the last GnRH antagonist dose and the agonist trigger within the first half-life of the GnRH antagonist and in less than 12 h. In normogonadotrophic patients, a GnRH agonist trigger can successfully induce an effective LH surge and oocyte maturation and release, irrespective of the time interval between the last antagonist dose and the agonist trigger. Once confirmed by randomized clinical trials, these finding may simplify treatment, improve patients' convenience and promote patient adherence to treatment.

Ovarian stimulation for freeze-all IVF cycles: a systematic review.

BACKGROUND: Freeze-all IVF cycles are becoming increasingly prevalent for a variety of clinical indications. However, the actual treatment objectives and preferred treatment regimens for freeze-all cycles have not been clearly established. OBJECTIVE AND RATIONALE: We aimed to conduct a systematic review of all aspects of ovarian stimulation for freeze-all cycles. SEARCH METHODS: A comprehensive search in Medline, Embase and The Cochrane Library was performed. The search strategy included keywords related to freeze-all, cycle segmentation, cumulative live birth rate, preimplantation genetic diagnosis, preimplantation genetic testing for aneuploidy, fertility preservation, oocyte donation and frozen-thawed embryo transfer. We included relevant studies published in English from 2000 to 2018. OUTCOMES: Our search generated 3292 records. Overall, 69 articles were included in the final review. Good-quality evidence indicates that in freeze-all cycles the cumulative live birth rate increases as the number of oocytes retrieved increases. Although the risk of severe ovarian hyperstimulation syndrome (OHSS) is virtually eliminated in freeze-all cycles, there are certain risks associated with retrieval of large oocyte cohorts. Therefore, ovarian stimulation should be planned to yield between 15 and 20 oocytes. The early follicular phase is currently the preferred starting point for ovarian stimulation, although luteal phase stimulation can be used if necessary. The improved safety associated with the GnRH antagonist regimen makes it the regimen of choice for ovarian stimulation in freeze-all cycles. Ovulation triggering with a GnRH agonist almost completely eliminates the risk of OHSS without affecting oocyte and embryo quality and is therefore the trigger of choice. The addition of low-dose hCG in a dual trigger has been suggested to improve oocyte and embryo quality, but further research in freeze-all cycles is required. Moderate-quality evidence indicates that in freeze-all cycles, a moderate delay of 2-3 days in ovulation triggering may result in the retrieval of an increased number of mature oocytes without impairing the pregnancy rate. There are no high-quality studies evaluating the effects of sustained supraphysiological estradiol (E2) levels on the safety and efficacy of freeze-all cycles. However, no significant adverse effects have been described. There is conflicting evidence regarding the effect of late follicular progesterone elevation in freeze-all cycles. WIDER IMPLICATIONS: Ovarian stimulation for freeze-all cycles is different in many aspects from conventional stimulation for fresh IVF cycles. Optimisation of ovarian stimulation for freeze-all cycles should result in enhanced treatment safety along with improved cumulative live birth rates and should become the focus of future studies.

Modified natural-cycle cryopreserved embryo transfer: is a washout period needed after a failed fresh cycle?

RESEARCH QUESTION: Are the characteristics of the natural cycle or modified natural cycle (mNC), or live birth rates (LBR), affected by delaying frozen embryo transfer (FET) after a failed fresh IVF cycle? DESIGN: In a retrospective study, conducted at a university-affiliated tertiary centre, 198 women aged 18-45 years undergoing their first FET cycle after a failed fresh embryo transfer attempt using an mNC were evaluated. Cycles were divided according to the time interval between oocyte retrieval and the start of the FET cycle into the immediate FET group (<22 days) and the delayed FET group (≥22 days). The main outcome measures were ovulation day and LBR. RESULTS: The mean interval between oocyte retrieval and the start of the FET cycle was 15.6 ± 3.2 days in the immediate FET group and 84.8 ± 73.7 days in the delayed FET group (P < 0.001). Ovulation day was significantly delayed in the immediate FET group (day 17.1 ± 4.4 versus day 15.4 ± 3.7; P = 0.004). There was no difference between the immediate and delayed FET groups in terms of clinical pregnancy rate (CPR) (25.4% and 25.0%, respectively) or LBR (21.2% and 20.0%, respectively). CONCLUSIONS: Natural-cycle characteristics are similar in immediate and delayed cycles, except for a slight delay in ovulation day. Deferring mNC-FET after a failed fresh IVF cycle does not improve the reproductive outcome. These results should encourage patients and clinicians who want to proceed with FET immediately after failure of fresh IVF.

Screening for blood born viruses in assisted reproduction: is annual testing necessary?

PURPOSE: Screening for blood born viruses is routinely performed before fertility treatment in assisted reproduction technology (ART) clinics worldwide. It involves testing for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), among others. Identifying patients with positive viral screening allows to refer them and their partners for appropriate counseling and treatment. The need for repeat viral screening and its required frequency have never been clearly established. In Israel, viral screening is mandatory and is repeated annually. Our aim was to determine the prevalence of HBV, HCV, and HIV seroconversion in patients with negative screening upon initiation of ART treatment. METHODS: A retrospective analysis of viral screening tests of all fertility patients in a single assisted conception unit between 1997 and 2015. RESULTS: During the study period, 2844 patients were treated at our clinic, out of whom 1945 patients met the inclusion criteria. The average length of treatment was 1.61 ± 0.81 years, during which female patients underwent screening tests 2.6 ± 0.9 times, and male patients 2.3 ± 1.2 times. No case of seroconversion to any of the three viruses was noted during the entire study period, resulting a seroconversion rate of 0%. CONCLUSIONS: Primary infection with HBV, HCV, or HIV is an extremely rare event among Israeli infertile patients, and the risk for seroconversion in this population is practically nil. Annual screening of both partners leads to substantial costs and appears to be futile. Our results question the current practice and support increasing the interval between screening tests in low-risk populations.

Should ICSI be implemented during IVF to all advanced-age patients with non-male factor subfertility?

BACKGROUD: In order to maximize In vitro fertilization (IVF) success rates in advanced- age patients, it has been suggested to favor the use of intracytoplasmic sperm injection (ICSI) over conventional insemination (CI), with the notion that ICSI would serve as a tool to overcome interference in sperm oocyte interaction and sperm oocyte penetration issues that can be related to maternal age and are not due to sperm abnormalities. We therefore aim to evaluate the role of ICSI in the treatment of non-male factor infertile patients aged ≥35 in terms of fertilization and top-quality embryo rates. METHODS: In this retrospective cohort study, data were collected and analyzed for all patients with non-male factor infertility, aged ≥35 treated, undergoing their first IVF cycle attempt with 6 or more oocytes yield, in whom a 50% ICSI-CI division was performed. RESULTS: Five hundreds and four oocytes were collected from 52 eligible patients. Overall, 245 oocytes underwent ICSI and 259 oocytes underwent CI. The fertilization rate was 71.0% following ICSI, compared to 50.1% in the CI treated oocytes (P < 0.001). The top quality embryo rate was 62.8% following ICSI compared to 45.5% following CI (P < 0.001). Subdividing the study population to two age groups revealed that the above differences remained significant in patients aged 35-39 yrs., whereas in those aged 40-45 yrs., the differences were non-significant but still inclined in favor of ICSI. CONCLUSIONS: This study favors the use of ICSI in the older IVF population in order to increase both the fertilization rate and the number of top quality embryos that result per IVF cycle. Further studies are needed to establish our observations and use ICSI as the preferred approach to overcome egg sperm abnormal interactions related to advanced maternal age.

Assessment of a double freezing approach in the management of surplus embryos in IVF.

RESEARCH QUESTION: What pregnancy rates are achieved after transfer of cryopreserved double slow-frozen embryos in IVF cycles? Patients in whom surplus thawed cleaved embryos (day 2 or 3) were grown to the blastocyst stage, re-frozen and then re-thawed for transfer (double freezing) were included. DESIGN: Data were collected on all patients who had undergone the above procedure at the IVF unit of Assuta Ramat Hachayal Hospital, Tel Aviv, during a 7-year period. For each patient in the study group, the two-consecutive, matched-by-age patients treated with frozen-thawed single blastocyst transfer were selected to form a 2:1 ratio control group. All embryos were frozen using the slow freeze protocol. RESULTS: A total of 54 patients had 70 embryos that were re-frozen at the blastocyst stage. Twenty-eight of these blastocysts were thawed and 27 underwent transfer to 25 patients. A single embryo was transferred to 23 patients and two embryos were transferred to two patients. The survival rate of the second thawing was 96.4% (27/28). Clinical pregnancy rate was 16% (4/25) and implantation rate was 14.8% (4/27). In the study group, pregnancies were achieved in 22 out of the 25 patients using IVF treatment, indicating good receptivity of the uterus. In the control group, the implantation/pregnancy rates were significantly higher (44.2% [23/52]; P < 0.01). CONCLUSION: The transfer of twice slow-frozen and thawed embryos does not seem to be a beneficial approach in the planned management of cryopreserved surplus embryos owing to the low pregnancy rate achieved after transfer of the re-frozen blastocyst embryos.

Human chorionic gonadotropin serum levels following ovulation triggering and IVF cycle outcome.

PURPOSE: The clinical significance of serum hCG levels after ovulation triggering was studied previously with conflicting results. Our aim was to study the correlation of hCG levels on the day after ovulation triggering using recombinant hCG (r-hCG) with treatment outcome. METHODS: A prospective observational study of all fresh IVF/ICSI cycles in a single medical center, between January 2015 and June 2016, was performed. hCG serum levels were obtained 10-12 h following ovulation triggering with 250 mcg r-hCG. Clinical and laboratory outcome parameters were compared between cycles with serum hCG above and below median level. A multivariate regression analysis was performed in order to study the association between hCG levels and live birth rate, after controlling for confounders. RESULTS: Overall, 326 cycles were included. Median serum hCG level was 91.35 IU/L. hCG levels were lower as age and BMI were higher (p = 0.004, p < 0.001, respectively). The study groups did not differ with regard to clinical pregnancy rate (p = 0.14), live birth rate (p = 0.09), fertilization rate (p = 0.45), or metaphase II oocyte rate (p = 0.68). On multivariate regression analysis, hCG level was not associated with live birth (aOR 0.99, 95% CI 0.98-1.005), after controlling for patient's age and BMI. CONCLUSIONS: hCG levels on the day after ovulation triggering with 250 mcg r-hCG are inversely correlated with patient age and BMI. However, they are not correlated with any clinical or laboratory outcome parameter. Therefore, testing for hCG levels after ovulation induction seems futile and cannot be recommended.

A previous caesarean section is not a risk factor for tubal abnormalities in the infertile population.

In this retrospective cohort study of 1716 cases of women undergoing infertility treatment between the years 1999-2012, we aimed to identify whether parturients with a previous surgical history are at a higher risk for tubal abnormalities as determined by hysterosalpingography (HSG) in this infertile population. Amongst the study population, tubal obstruction was identified on HSG in 15.8% of patients with no past history of an abdominal surgery and 16.3% of patients with a previous caesarean section (CS) delivery. These rates were significantly lower than those for women with a previous gynaecological surgery (34.7%) or abdominal surgery (27%) (p < .001 for all comparisons). Our results suggest that past history of CS poses no additional risk for tubal abnormality within the infertile population, whereas a history of other abdominal or gynaecological surgical procedures doubles this risk. Impact Statement What is already known on this subject? While numerous risk factors for tubal factor infertility have been established, to date, the relation between previous abdominal surgeries and the risk for tubal factor infertility remains inconclusive. What the results of this study add? In this study, we aimed to evaluate the correlation between previous CS history and the risk for having tubal factor infertility. Our results demonstrated that previous caesarean section delivery does not increase the risk for tubal factor infertility in the infertile population, whereas history of other abdominal or gynaecological surgical procedures doubles this risk. What the implications are of these findings for clinical practice and/or further research? Further research is needed for further evaluation of this association and its clinical implications.

Short-term exposure of human ovarian follicles to cyclophosphamide metabolites seems to promote follicular activation in vitro.

How chemotherapy affects dormant ovarian primordial follicles is unclear. The 'burnout' theory, studied only in mice, suggests cyclophosphamide enhances primordial follicle activation. Using 4-hydroperoxycyclophosphamide (4hc) and phosphoramide mustard (PM), this study assessed how the active cyclophosphamide metabolites 4-hydroxycyclophosphamide (4-OHC) and PM, affect human primordial follicles. Frozen-thawed human ovarian samples were sliced and cultured with basic culture medium (cultured controls) or with 4hc/PM (3 µmol/l/10 µmol/l) (treated samples) for 24-48 h. Follicular counts and classification, Ki67 and anti-Müllerian hormone (AMH) immunohistochemistry and an apoptosis assay were used for evaluation, and 17ß-oestradiol and AMH were measured in spent media samples. Generally, there was primordial follicle decrease and elevated developing follicle rates in treated samples compared with cultured (P = 0.04 to P < 0.0005) and uncultured controls (P < 0.05 to P < 0.0001). No traces of apoptosis were found. There were almost twicethe levels of AMH and 17ß-oestradiol in treated compared with untreated samples (AMH with 4hc 3 µmol/l; P = 0.04). All follicles stained positively for AMHincluded treated samples. Ki67 positive staining was noted in all samples. Cyclophosphamide metabolites seem to enhance human primordial follicle activation to developing follicles, in vitro. Study findings support the 'burnout' theory as the mechanism of chemotherapy-induced ovarian toxicity.

Correlations between antral follicle count and ultrasonographic ovarian parameters and clinical variables and outcomes in IVF cycles.

AIMS: To assess the correlation between the antral follicle count (AFC) and other ultrasonographic parameters and clinical variables in in vitro fertilization (IVF) cycles. METHODS: Pretreatment ultrasonographic evaluation included AFC (total), large (5-10 mm) and small (2-4 mm) antral follicles, ovarian volume, and ovarian Doppler indices. Data were prospectively uploaded and subsequently analysed in relation to IVF cycle results. RESULTS: The study included 128 women (128 cycles). Analysis of body mass index (BMI) yielded a weak significant correlation with large (5-10 mm) AFC but not with other sonographic variables. AFC was significantly correlated with patient age, ovarian volume, number of retrieved oocytes, total dose of used gonadotropins, peak estradiol, number of top-quality embryos, and number of frozen embryos and marginally correlated with number of aspirated immature oocytes. Lower large (5-10 mm) AFC was the only ovarian parameter associated with oral contraception pretreatment compared to nontreatment, even after adjustment for age and BMI. There was no difference in any of the parameters between short and long IVF cycles. CONCLUSIONS: BMI is only weakly correlated with AFC. Pretreatment with oral contraceptives may be associated with lower AFC. Pretreatment with gonadotropin-releasing hormone agonist (long protocol) does not alter the ultrasonographic ovarian parameters.

Novel protocol for scheduling oocyte retrieval in IVM cycles in PCOS patients: a case series.

In-vitro maturation (IVM) is associated with a longer egg-collection procedure in the operating room and a longer oocyte-handling time in the IVF laboratory than standard IVF. Hence, if the designated day of oocyte retrieval could be planned in advance, the workload pressure on that specific day can be planned in advance. This study presents a simple method for advance scheduling of IVM in patients with polycystic ovary syndrome (PCOS). A fixed protocol of oral contraceptive pill administered prior to gonadotrophin priming and based on the days of the week enable the exact dating of the oocyte retrieval day, thereby increasing patient convenience and improving control of the IVF-unit workload. This protocol was compared with immediate-start IVM and resulted in a similar pregnancy rate (43.8% and 40.0% per cycle, respectively).

Small antral follicle count (2-5 mm) and ovarian volume for prediction of pregnancy in in vitro fertilization cycles.

AIMS: To assess the value of antral follicle count (AFC) and other parameters as predictors of pregnancy in in vitro fertilization (IVF). METHODS: In a cohort study, unselected consecutive women in IVF treatment were evaluated. Pretreatment parameters included AFC (subpopulations of small (2-5 mm) and large (5-10 mm) AFC), ovarian volume, and ovarian stroma Doppler indices. RESULTS: The study included 115 women of whom 38 (33%) were pregnant. Total AFC was significantly higher in the pregnant than in the non-pregnant group (13.7 ± 5.8 vs. 11.3 ± 5.3, p = 0.034). On receiver operator characteristic (ROC) curve analysis, the pretreatment variables that were significantly associated with pregnancy were small AFC (2-5 mm), total AFC, and ovarian volume/AFC ratio. Women with a positive score (total AFC >15; small AFC (2-5 mm) >10; ovarian volume in mm(3)/AFC, <1400), had a significantly higher number of retrieved oocytes and a higher pregnancy rate than women with a negative score (12.1 ± 5.1 vs. 8.7 ± 5.0, p = 0.027 and 58.3% vs. 30.1%, p = 0.049, respectively). On multivariate logistic regression analysis, total AFC was the only significant and independent predictor of pregnancy (p = 0.034). CONCLUSION: Pretreatment small AFC and ovarian volume may identify women with a higher probability to achieve pregnancy in IVF.