A clinical predictive model for live birth in women of advanced age undergoing PGT cycles.

PURPOSE: The trend of delaying childbirth has resulted in a growing number of advanced-aged women who are opting for preimplantation genetic testing (PGT) to screen for monogenic diseases or structural chromosomal rearrangements (PGT-M and PGT-SR). This increase in demand necessitates the development of a clinical predictive model for live birth outcomes in these women. Therefore, the objective of this study is to construct a comprehensive predictive model that assesses the likelihood of achieving a successful live birth in advanced-aged women undergoing PGT-M and PGT-SR treatments. METHODS: A retrospective cohort study of 37-45-year-old women undergoing preimplantation genetic testing for monogenic disease or structural chromosomal rearrangement cycles from 2010 to 2021 was conducted at a university hospital reproductive centre. The purpose was to develop a clinical predictive model for live birth in these women. The main outcome studied was the cumulative live birth rate in the first or subsequent cycles. Developing a decision tree enabled a comprehensive study of clinical parameters and expected outcomes. RESULTS: The analysis included 158 women undergoing 753 preimplantation genetic testing cycles. The cumulative live birth rate was 37.342% (59/158). Decision tree analysis revealed that women aged ≤ 40.1 or women > 40.1 with one or more top-quality transferable embryos in their first cycle had the best chance for a live baby (56% and 41%, respectively). Those older than 40.1 without top-quality embryos and seven or fewer dominant follicles had no live births. A Kaplan-Meier curve showed that for autosomal dominant diseases, there was a negligible increase in live birth rate after three cycles, compared to six cycles in autosomal recessive inheritance. CONCLUSION: In older women, the chance of delivering after repeated cycles is higher in those with at least one top-quality unaffected embryo in their first preimplantation genetic testing cycle. Additional preimplantation genetic testing cycles after three in carriers of an autosomal dominant disorder and six in those with an autosomal recessive disorder should be considered prudently.

Intra-patient analysis of individual weight gain or loss between IVF cycles: cycle now and transfer later.

STUDY QUESTION: What is the impact of clinically significant weight change on outcomes related to IVF cycle performance? SUMMARY ANSWER: While individual weight loss did not significantly impact ovarian response to stimulation or other cycle outcome parameters in our study, some positive associations were found for individual weight gain. WHAT IS KNOWN ALREADY: The role of weight-change in patients undergoing IVF has been largely studied by comparing weight loss in different cohorts of patients stratified by a static BMI. Specifically, obesity has been extensively studied in relation to its negative effects on assisted or unassisted conception outcomes and ovulatory function. Previous research has shown conflicting results, while BMI, which is commonly used as a marker of obesity, may not accurately reflect the underlying factors affecting fertility in obese patients. STUDY DESIGN, SIZE, DURATION: This study utilized a retrospective within-patient repeated measurement analysis design to assess the impact of weight change on IVF outcomes in cycles where all embryos were cryopreserved at the blastocyst stage for transfer at a later date. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at an academically affiliated fertility center. The data included 961 women who underwent at least two IVF cycles between December 2014 and June 2020, with documented short-term weight gain (n = 607) or weight loss (n = 354) within 1 year from their initial IVF cycle. Multivariable generalized estimating equations (GEE) and generalized linear mixed models (GLMM) were employed to assess associations between weight change and outcomes across cycles. MAIN RESULTS AND THE ROLE OF CHANCE: The multivariable models indicated that weight loss did not show any significant associations with the numbers of oocytes retrieved, or mature oocytes, the fertilization rate or the blastulation rate. However, weight gain demonstrated a minor positive association with the number of oocytes retrieved in both GEE models (coefficient: 0.01, 95% CI: 0.00-0.01) and GLMM models (0.01, 95% CI: 0.01-0.00). There was also a potential increase in the fertilization rate with weight gain, as indicated by a positive coefficient in both GEE models (coefficient: 0.01, 95% CI: 0.00-0.02) and GLMM models (coefficient: 0.01, 95% CI: 0.00-0.01). However, the association between weight gain and the embryo blastulation rate was not statistically significant in any model. LIMITATIONS, REASONS FOR CAUTION: This study focused on cycle performance parameters instead of reproductive outcomes, which restricted our ability to evaluate the impact of weight change on cumulative live birth rates. Additionally, the study did not account for variables such as stimulation protocols, potentially introducing confounding factors and limiting the generalizability of the results. WIDER IMPLICATIONS OF THE FINDINGS: Although obesity is associated with adverse obstetrical risks, there is less evidence of adverse reproductive outcomes in IVF cycles. We therefore recommend that an IVF cycle should not be delayed due to weight, so that the patient is not adversely affected by increasing age. The IVF cycle should aim to freeze all embryos, so that embryo transfer can then occur after weight loss, so as to limit the recognized obstetrical risks. STUDY FUNDING/COMPETING INTEREST(S): The study was not funded and there were no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Prognostic factors for spontaneous resolution of an ectopic pregnancy.

OBJECTIVE: To identify factors that can accurately predict the spontaneous resolution of an ectopic pregnancy. STUDY DESIGN: This retrospective cohort analysis was conducted in the Department of Gynecology of a tertiary, university-affiliated medical center. Patients admitted to the center from January 2015 to July 2022 with a tubal ectopic pregnancy who met the criteria for expectant management were included. Beta-human chorionic gonadotropin (ß-hCG) levels were assessed at admission and at subsequent 24-hour intervals. Patients with declining levels were discharged for routine ambulatory ß-hCG follow-up until levels became undetectable. Patients who achieved a successful outcome were designated as the "spontaneous resolution group," while patients who underwent further hospitalization for methotrexate or surgery constituted the" failure group". Demographic, clinical, laboratory, and ultrasound parameters collected at first admission were compared between groups. RESULTS: Among the initial group of 210 eligible patients, 7 were lost to follow-up, 161 achieved spontaneous resolution, and 42 were readmitted for active intervention. Multivariate logistic regression analysis revealed that the last ß-hCG level before discharge (last ß-hCG) and the ratio between ß-hCG at discharge to ß-hCG at admission were the only independent parameters to predict outcomes. Patients with ß-hCG < 650 IU/L at discharge and a decline of 50% or more in ß-hCG level during hospitalization, had a 97% success rate with expectant management. Patients with ß-hCG discharge levels ≥ 1,000 IU/L had a 50% chance of success, regardless of whether their ß-hCG levels had declined. For all other patients, a 76% success rate was found. CONCLUSION: Short-term, serial ß-hCG follow-up at the initial presentation can help predict the spontaneous resolution of an ectopic pregnancy.

Estimating predictors of severity of group A Streptococcus infection in pregnancy.

OBJECTIVE: To identify the clinical characteristics of pregnancy associated group A streptococcus (GAS) infection and predictors for intensive care unit (ICU) admission. METHODS: A retrospective cohort study of culture-proven pregnancy-related GAS infections in tertiary hospital Electronic medical records were reviewed, for cases of cultures positive GAS that were identified between January 2008 and July 2021. A GAS infection was defined by the isolation of the pathogen from a sterile liquid or tissue site. Blood and urine cultures were obtained from all patients with peripartum hyperpyrexia (fever >38 °C). Medical Personnel screening included cultures of the throat, rectum, and skin lesions (if present). In cases of hemodynamic instability patients were transferred ad hoc to ICU, according to the obstetrician and intensivist judgment. RESULTS: Of the 143,750 who delivered during the study period, 66 (0.04%) were diagnosed as having a pregnancy associated GAS infection. Of these, 57 patients presented postpartum, and represented the study cohort. The most common presenting signs and symptoms among puerperal GAS, were postpartum pyrexia (72%), abdominal pain (33%), and tachycardia (>100 bpm, 22%). 12 women (21.0%) developed streptococcal toxic shock syndrome (STSS. Predictors for STSS and ICU admission were: antibiotic administration >24 h from presentation postpartum, tachycardia, and a C-reactive protein level >200 mg/L. Women that received antibiotic prophylaxis during labor had a significantly lower rate of STSS (0 vs 10, 22.7%; p = .04). CONCLUSION: Deferral of medical intervention >24 h from the first registered abnormal sign had the most important impact on deterioration of women with invasive puerperal GAS. Antibiotic prophylaxis during labor in women with GAS may reduce associated complications.

Fertility Preservation in Endometriosis: Does Patient Symptomatology Affect the Extent of the Ovarian Response?

This study is to identify factors and patient symptomatology affecting ovarian response in women with endometriosis who seek fertility preservation. An observational cross-sectional study was conducted from July 2017 to May 2020 at a tertiary university-affiliated medical center. We included patients who were treated in the endometriosis clinic and underwent fertility preservation. Patients completed an online questionnaire that was cross-referenced with electronic charts. An analysis related to patient data and fertility preservation cycles and a mediation analysis were performed. The mean patient age at time of fertility preservation was 35.2 (± 4.9) years. The mean accumulated number of oocytes vitrified per patient was 16.7 (± 12.1) oocytes. The correlation coefficient assessed between the number of oocytes vitrified per cycle and AMH was significantly positive at +0.472, p = 0.006. The examined reported symptoms were lethargy, chronic pelvic pain, dyschezia, dyspareunia, bowel-associated symptoms, and urinary tract symptoms. The number of oocytes vitrified correlated with the number of reported symptoms and clinical characteristics at - 0.497, p = 0.0001, and - 0.442, p = 0.0001, respectively. In a mediation analysis, the potential causality of surgical intervention in the relationship between the number of symptoms and ovarian response was - 0.300 (95% CI [0.15, 1.905], p = 0.05), and the calculated proportion of mediation was estimated to be 17%. We observed a significant negative association between the number of clinical symptoms and the quantity of vitrified oocytes. This relationship was only partly associated with prior surgical intervention. AMH was found to have the highest correlation with treatment success in patients with endometriosis undergoing fertility preservation.

The association between a carrier state of FMR1 premutation and numeric sex chromosome variations.

PURPOSE: Women carriers of FMR1 premutation are at increased risk of early ovarian dysfunction and even premature ovarian insufficiency. The aim of this study was to examine a possible association between FMR1 permutation and numeric sex chromosome variations. METHODS: A retrospective case-control study conducted in the reproductive center of a university-affiliated medical center. The primary outcome measure was the rate of sex chromosomal numerical aberrations, as demonstrated by haplotype analyses, in FMR1 premutation carriers compared to X-linked preimplantation genetic testing for monogenic/single gene defect (PGT-M) cycles for other indications that do not affect the ovarian follicles and oocytes. RESULTS: A total of 2790 embryos with a final genetic analysis from 577 IVF PGT-M cycles were included in the final analysis. Mean age was similar between the groups, however, FMR1 carriers required more gonadotropins, and more women were poor responders with three or less oocytes collected. The ratio of embryos carrying a numeric sex chromosome variation was similar: 8.3% (138/1668) of embryos in the FMR1 group compared to 7.1% (80/1122) in the controls. A subgroup analysis based on age and response to stimulation has not demonstrated a significant difference either. CONCLUSIONS: Although carriers of FMR1 premutation exhibit signs of reduced ovarian response, it does not seem to affect the rate of numeric sex chromosomal variation compared to women undergoing PGT-M for other indications. This suggests that the mechanism for chromosomal number aberrations in women at advanced maternal age are different to those FMR1 premutation carriers with poor ovarian reserve.

Reproductive Outcomes and Overall Prognosis of Women with Asherman's Syndrome Undergoing IVF.

STUDY OBJECTIVE: To evaluate the impact of Asherman syndrome (AS) following hysteroscopic adhesiolysis on reproductive outcomes and the time to achieve pregnancy in women with infertility undergoing in vitro fertilization (IVF) treatment. DESIGN: Case-control study. SETTING: Tertiary university-affiliated medical center. PATIENTS: Fifty-one infertile women who were treated for AS and underwent IVF (study group) matched for age and etiology of infertility with non-AS controls at a 1:1 ratio. INTERVENTIONS: Medical records search, chart review, and phone survey were used to assess reproductive outcomes. MEASUREMENTS AND MAIN RESULTS: A multivariate logistic regression analyses was used to assess live birth, accounting for patient age at stimulation cycle start, parity, number of embryos transferred, and endometrial thickness. A survival analysis was performed to assess the times that had lapsed from interventions to conception. The study group of 51 women included 38 (74.5%) with moderate to severe disease. The mean number of embryo transfers per woman was similar for the study and control groups (4.9 ± 4.6 vs 6.22 ± 4.3, respectively, p = .78). The controls had a significantly higher mean endometrial thickness before embryo transfer (8.7 ± 1.8 mm vs 6.95 ± 1.7 mm, p = .001). The overall time to achieve live birth was significantly longer in women with AS (p = .022). In a logistic regression analysis, the presence of moderate to severe AS was shown to be an independent factor for achieving a live birth (adjusted odds ratio 0.174, 95% confidence interval [CI], 0.032-0.955, p = .004). Women with AS who had live births had a significantly thicker mean endometrial thickness (8.2 ± 1.4 mm vs 6.9 ± 1.2, p = .001). CONCLUSION: Moderate and severe AS has a detrimental effect on reproductive performance in infertile women. Endometrial thickness is an important predictor for live births among women with AS who undergo IVF.

The impact of fragile X premutation carrier status on embryo morphokinetic development.

RESEARCH QUESTION: Does inheritance of the fragile X mental retardation 1 (FMR1) premutation allele affect embryo morphokinetic development? DESIGN: A retrospective cohort analysis of 529 embryos from 126 IVF cycles of 39 FMR1 premutation female carriers undergoing preimplantation genetic testing for monogenic/single gene defects (PGT-M). Morphological and morphokinetic parameters obtained using a time-lapse monitoring system were compared between embryos that inherited the FMR1 premutation allele (FMR1 group, n = 271) and those who received the normal allele (normal group, n = 258). The following embryo outcome measures were compared: morphokinetic parameters up to day 3, start of blastulation time (tSB) for day 5 embryos and the rate of top-quality embryos on days 3 and 5. RESULTS: No differences were found in morphokinetic parameters between the groups from the time of intracytoplasmic sperm injection (ICSI) until a biopsy on day 3. The blastulation rate in the two groups was comparable. However, the start of blastulation was delayed in FMR1 embryos compared to that in the genetically normal embryos (median tSB: 104.2 h [99.3-110.3] versus 101.6 h [94.5-106.7], P = 0.01). In addition, the rate of top-quality FMR1 embryos was lower than that of genetically normal embryos (25.6% versus 38.8%, P = 0.04). CONCLUSION: Embryos that inherit the FMR1 premutation allele are of lower quality at the blastocyst stage compared with those that do not inherit the mutated allele.

Ruptured ectopic pregnancies following methotrexate treatment: clinical course and predictors for improving patient counseling.

To determine the predictors for tubal rupture among women treated with methotrexate (MTX) for ectopic pregnancy. We performed a retrospective cohort analysis in a tertiary university-affiliated medical center. Medical records of 401 women who were diagnosed with ectopic pregnancy and were treated with MTX between January 2001 and June 2017 were reviewed. Forty-one women were diagnosed with ruptured ectopic pregnancy (study group) and 360 women with non-ruptured ectopic pregnancy (control group). Descriptive data and predictive variables for rupture ectopic pregnancy following MTX treatment were reviewed. Out of 122 women who failed MTX treatment, forty-one women had tubal rupture (33.6%). The median time interval from MTX treatment to tubal rupture was 6 days (1-25). ß-hCG percentage change in the 48 h preceding MTX treatment and ß-hCG level at day 0 were independent predictors for tubal rupture (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.04-1.12, p < 0.001 for every percent change in ß-hCG; OR = 1.001, 95% CI = 1.0003-1.002 for every unit change in ß-hCG, respectively). In a decision tree analysis model, in women with ß-hCG percentage increment >69% in the 48 h preceding methotrexate the probability for tubal rupture was 85%. Risk assessment for tubal rupture should be made before methotrexate treatment according to ß-hCG dynamics and level. The absolute risk for tubal rupture in women with ß-hCG increment<20% is low.

A decision tree analysis applied to women aged 43-45: who should be referred for ovum donation?

RESEARCH QUESTION: In women at the advanced age of 43-45 years undergoing repeated IVF cycles with autologous oocytes, who has the highest chance for birth and who should be referred early to receive donor oocytes? DESIGN: A retrospective cohort study was conducted at a university hospital reproductive centre. The computerized database of 394 women aged 43-45 years undergoing 1528 non-donor IVF or intracytoplasmic sperm injection cycles between 2010 and 2019 was analysed. A decision tree was developed, enabling a comprehensive study of a set of clinical parameters and the expected outcomes. RESULTS: The cumulative clinical pregnancy rate was 15.0% (59/394) and the cumulative live birth rate was 8.4% (33/394). The decision tree developed to predict women who should be offered egg donation included age, poor ovarian response to stimulation, the number of top-quality embryos, dominant follicles, previous pregnancy or live birth, fertilized oocytes and body mass index. The model showed that a good ovarian response in the first cycle was the best predictor for live birth (13.3% gave birth). However, among women with poor responses, 7.1% of those who were younger than 43.5 years gave birth, and none of the women who were older than 43.5 years did. CONCLUSIONS: Women over 43.5 years old with fewer than four oocytes collected in their first IVF cycle should be offered ovum donation, since their live birth rate in subsequent cycles is negligible.

Preimplantation genetic testing for BRCA gene mutation carriers: a cost effectiveness analysis.

BACKGROUND: Gynecologic oncologists should be aware of the option of conception through IVF/PGT-M for families with high BRCA related morbidity or mortality. Our objective was to investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception. METHODS: Cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality adjusted life years (QALYs'). All costs were discounted at 3%. Incremental cost effectiveness ratio (ICER) compared to willingness to pay threshold was used for cost-effectiveness analysis. RESULTS: IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate. CONCLUSIONS: IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is cost effective and may be offered for selected couples with high BRCA mutation related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers.

A decision tree model for predicting live birth in FMR1 premutation carriers undergoing preimplantation genetic testing for monogenic/single gene defects.

RESEARCH QUESTION: Can patient selection for successful preimplantation genetic testing for women who are fragile X (FMR1) premutation carriers be optimized using a decision tree analysis? This decision support tool enables a comprehensive study of a set of clinical parameters and the expected outcomes. DESIGN: A retrospective case-control study analysing the results of 264 fresh and 21 frozen preimplantation genetic testing for monogenic disorders/single gene defects (PGT-M) cycles in 64 FMR1 premutation carriers. Primary outcome was live birth per cycle start. Live birth rate was calculated for the start of the ovarian stimulation cycle. Fresh and frozen embryo transfers from the same cycle were included. RESULTS: The decision tree model showed that the number of cytosine guanine (CGG) repeats was only a moderate predictor for live birth, whereas an age younger than 36 years was the best predictor for live birth, followed by a collection of 14 or more oocytes. These findings were supported by the results of the logistic regression, which found that only age and oocyte number were significantly associated with live birth (P = 0.005 and 0.017, respectively). CONCLUSIONS: The number of CGG repeats is a relatively poor predictor for live birth in PGT-M cycles. FMR1 premutation carriers are no different from non-carriers. Age is the best identifier of live birth, followed by the number of retrieved oocytes.

Effects of letrozole or tamoxifen coadministered with a standard stimulation protocol on fertility preservation among breast cancer patients.

PURPOSE: To assess the effects of letrozole or tamoxifen coadministration on fertility preservation treatment outcomes. METHODS: Retrospective cohort study of 118 breast cancer patients undergoing fertility preservation treatment between 2008 and 2018. Patients who received letrozole (n = 36) or tamoxifen (n = 30) were compared to controls (n = 52) who underwent standard ovarian stimulation protocols. The primary outcome measures included the number of retrieved oocytes, mature oocytes (MII), fertilization, and top-quality embryo rates. The secondary outcome measures included duration of stimulation, gonadotropin dose and peak estradiol level. RESULTS: The number of oocytes retrieved, MII oocytes, fertilization rate, duration of stimulation, or gonadotropin dose were similar in the letrozole and tamoxifen groups, compared to controls. Top-quality embryo rate was lower in the tamoxifen group compared to controls (25% vs 39.4%, respectively, P = 0.034). The abnormal fertilization rate was higher in the letrozole group compared to controls (7.8% vs 3.60%, respectively, P = 0.015). A stepwise logistic regression analysis revealed that letrozole and peak estradiol were significantly associated with abnormal fertilization (OR 11.94; 95% CI 2.35-60.4, P = 0.003 for letrozole and OR 1.075; 95% CI 1.024-1.12, P = 0.004 per 100 unit change in estradiol). CONCLUSIONS: There may be a negative effect of letrozole or tamoxifen on fertilization and embryo quality, in fertility preservation cycles. Further studies are needed to confirm these findings.

In-vitro maturation of oocytes recovered during cryopreservation of pre-pubertal girls undergoing fertility preservation.

RESEARCH QUESTION: In-vitro maturation (IVM) of oocytes recovered during ovarian tissue cryopreservation (OTC) is often practised, although it is still considered experimental. To date, only a few studies have examined the success of this maturation process in pre-menarche girls. The aim of this study was to examine the outcomes of IVM of oocytes recovered during OTC in pre-menarche patients scheduled for onco-therapy. DESIGN: A retrospective cohort study in a tertiary university-affiliated hospital. A total of 93 patients aged 0-25 years who underwent OTC as part of onco-fertility preservation between 2007 and 2019 were included in the study. Oocytes were recovered from the medium after OTC and matured over 48 h. Oocyte development and maturation rate were recorded and compared between different age groups. RESULTS: Patient's age was not correlated linearly with the total number of mature oocytes R = 0.2. The absolute maturation rate in post-menarche and pre-menarche patients differed significantly (38.0% versus 25.3%, respectively; P > 0.001), whereas the degeneration rate of the oocytes did not (39.8% versus 33.5%; P = 0.167). The pre-menarche group had significantly lower mean number of metaphase II oocytes compared with the post-menarche group (2.8 [±2.3] versus 5.6 [±4.6]; P = 0.01; 95% CI -4.62 to -0.46). Oocytes recovered from patients aged 1-5 years demonstrated low maturation rate. CONCLUSIONS: Oocytes recovered from pre-menarche girls, and especially those younger than the age of 5 years who undergo fertility preservation, have a lower chance of reaching maturity in IVM compared with older women. This may indicate a need for alternative methods for preserving fertility in these young patients.

Added Benefit of Immature Oocyte Maturation for Fertility Preservation in Women with Malignancy.

To assess the added value of maturing immature oocytes collected during fertility preservation treatments in women with malignancy. A retrospective case-control study analyzing the results of 327 cancer patients undergoing fertility preservation treatments. Oocyte maturation rates and cycle parameters were compared between 3 types of fertility preservation treatments: (1) stimulated IVF cycle (n = 143), (2) non-stimulated IVM cycle (n = 158), (3) follicle aspiration and oocyte collection from ovarian tissue prepared for ovarian tissue cryopreservation followed by in vitro maturation of the immature oocytes (n = 48). The primary outcome measure was the maturation rate and the number of mature oocytes. The secondary outcomes were oocyte fertilization and embryo development rates. The mean maturation rate in IVF cycles was 38% and in the non-stimulated IVM cycles was 55%. In women who chose to cryopreserve their embryos, similar fertilization and embryo cleavage rates were found in oocytes that matured after stimulated IVF cycles compared to non-stimulated IVM cycles. Gonadotropin-releasing hormone agonist triggering, treatment with aromatase inhibitor, or oral contraceptives use before the cycle did not affect the maturation rate. Ovarian stimulation yields the highest number of oocytes or embryos for cryopreservation. Although the maturation rate of immature oocytes collected in stimulated IVF cycles is low, it is still a viable source of oocytes that can be used to improve the efficacy of fertility preservation treatments by increasing the number of mature oocytes available for freezing or fertilization.

The Role of Fertility Preservation in Women with Endometriosis: A Systematic Review.

OBJECTIVE: To summarize the available evidence concerning fertility preservation techniques in the context of women with endometriosis. DATA SOURCES: We searched for studies published between 1984 and 2019 on endometriosis and Assisted Reproductive Technology outcomes. We searched MEDLINE and PubMed and performed a manual search of reference lists within identified studies. METHODS OF STUDY SELECTION: A total of 426 articles were identified, and 7 studies were eligible to be included for the systematic review. We included all published studies, excluding reviews, case reports, and animal studies. TABULATION, INTEGRATION, AND RESULTS: Despite a significant increase in the number of studies addressing fertility preservation over the study period, we found a relative lack of evidence addressing the use of fertility preservation techniques in women with endometriosis. The studies identified included 2 case reports, 1 histological science study, and 4 retrospective cohort studies. CONCLUSION: Women with endometriosis may benefit from fertility preservation techniques. However, there currently is a paucity of data in this population, especially when compared with other indications for fertility preservation. Although much knowledge can be translated from the oncofertility discipline, we have identified and discussed endometriosis-related changes to ovarian reserve and oocyte health that justify further well-designed research to confirm that fertility preservation outcomes are similar for women with endometriosis.

Immature Oocyte for Fertility Preservation.

In vitro maturation (IVM) of human immature oocytes has been offered to women who are at risk of developing ovarian hyperstimulation syndrome (OHSS) caused by gonadotropin stimulation, such as PCO(S) patients or who have poor ovarian reserve. Cryopreservation of oocytes matured in vivo obtained in IVF cycles has improved after implementing the vitrification method and many successful results have been reported. Now, this procedure can be successfully offered to fertility preservation programs for patients who are in danger of losing their ovarian function due to medical or social reasons, and to oocyte donation programs. This vitrification technique has also been applied to cryopreserve oocytes obtained from IVM program. Some advantages of oocytes vitrification related with IVM are: (1) eliminating costly drugs and frequent monitoring; (2) completing treatment within 2 to 10 days (3) avoiding the use of hormones in cancer patients with hormone-sensitive tumors; and (4) retrieving oocytes at any point in menstrual cycle, even in the luteal phase. In addition, immature oocytes can also be collected from extracorporeal ovarian biopsy specimens or ovaries during caesarian section. Theoretically, there are two possible approaches for preserving immature oocytes: oocyte cryopreservation at the mature stage (after IVM) and oocyte cryopreservation at the Germinal Vesicle (GV)-stage (before IVM). Both vitrification of immature oocyte before/after IVM is not currently satisfactory. Nevertheless, many IVF centers worldwide are doing IVM oocyte cryopreservation as one of the options to preserve fertility for female cancer. Therefore, more studies are urgently required to improve IVM- and vitrification method to successfully preserve oocytes collected from cancer patients. In this review, present oocyte maturation mechanisms and recent progress of human IVM cycles will be discussed first, followed by some studies of the vitrification of human IVM oocyte.

Fertility outcomes in patients with tubo-ovarian abscesses after an oocyte retrieval: a longitudinal cohort analysis.

PURPOSE: To determine the impact of pelvic inflammation caused by tubo-ovarian abscess (TOA) on ovarian response to stimulation. METHODS: This retrospective longitudinal cohort analysis that was carried out in a tertiary university-affiliated medical center included 15 women with TOA during in vitro fertilization (IVF) cycles. The ovarian response to stimulation and the pregnancy rate were compared in two subsequent cycles, the initial IVF cycle that was complicated by TOA after oocyte retrieval (first treatment cycle) and the following IVF treatment (second treatment cycle) that occurred within a period of a year from the first cycle. RESULTS: The mean number of retrieved oocytes was significantly higher in the first IVF cycle compared to the second cycle (8.1 ± 3.2 vs. 5.4 ± 2.5, P = .003], corresponding to a 30% reduction in ovarian response to gonadotropin stimulation. Fertilization rates were significantly lower in the second cycle (4.1 ± 2.9 vs. 2.9 ± 1.7, P = .015). Twelve women (80%) reached embryo transfer in the first cycle compared to 14 women (93.3%) in the second cycle. The mean number of transferred embryos was similar between the two cycles. There were no clinical pregnancies following the first cycle, and only one patient (6.6%) had a clinical pregnancy in the second treatment cycle. CONCLUSIONS: TOA following fertility treatment has a detrimental effect on ovarian function. The pregnancy rate in the immediate period following TOA is poor. Current data for recommending the deferral of fertility treatment following a TOA episode are insufficient, calling for more studies to address these issues.

Effects of cancer stage and grade on fertility preservation outcome and ovarian stimulation response.

STUDY QUESTION: Do the stage and grade of malignancy affect the fertility preservation outcome in females? SUMMARY ANSWER: Patients with high-grade cancer have a decreased number of retrieved mature oocytes and cryopreserved embryos. WHAT IS KNOWN ALREADY: Cancer has local and systemic effects on the host. The effects of cancer spread and aggressiveness on the ovarian function and stimulation response remain unclear. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study evaluating data of all fertility preservation treatment cycles among women with cancer at the reproductive unit of the McGill University Health Centre in the period from 2008 to 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Study inclusion criteria were age 18-38 years, first stimulation cycle, GnRH-antagonist protocol and early follicular phase stimulation start. Only one stimulation cycle per patient was included. Patients with ovarian pathology, previous ovarian surgery and previous chemo- or radiotherapy were excluded. The outcomes of women with low-stage cancer (local tumor Stage I-II, no lymph node involvement, no metastases) were compared with those with high-stage disease (local tumor Stage III-IV, lymph node involvement or metastases). Similarly we compared those with low-grade (G1-2) and high-grade (G3-4) malignancies. The primary outcome measure was the number of mature oocytes retrieved. The secondary outcomes included the total number of retrieved oocytes, the number of vitrified oocytes, and the number of frozen embryos. We used Student's t-test for normally distributed data and Wilcoxon test for skewed data. To determine factors associated with good fertility preservation outcome defined as over 10 retrieved mature oocytes, we used multivariate logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 147 patients were included in the final analysis. Age, body mass index, ovarian reserve parameters of the study groups in stage- and grade-based analyses were similar. Compared to women with low-stage cancer (n = 83), those with high-stage cancer (n = 64) required a higher dose of gonadotropin (P = 0.02). The number of retrieved mature oocytes (9 (7-13) versus 8 (5-12); P = 0.37) and vitrified oocytes (10 (7-15) versus 10 (7-13); P = 0.53) were similar between the two groups. However, in cycles where fertilization of all retrieved oocytes was performed, the fertilization rate (82.7% versus 71.5%; P = 0.03) and the number of vitrified embryos (6.2 ± 3.2 versus 4.3 ± 2.1; P = 0.01) were higher in the low-stage group. Compared to patients with low-grade cancer (n = 62), those with high-grade disease (n = 85) had significantly lower number of retrieved mature oocytes (11 (7-15) versus 8 (5-11); P = 0.002) and vitrified oocytes (12 (8-15) versus 10 (7-11); P = 0.005). The number of vitrified embryos was lower in high-grade group (6.5 ± 3.5 versus 4.6 ± 2.3; P = 0.03) in cycles where the fertilization was performed. In multivariate logistical analysis, the low-grade cancer was significantly associated with retrieval of over 10 mature oocytes (OR = 4.26; 95% CI 1.82-9.98; P = 0.0009). LIMITATIONS, REASONS FOR CAUTION: The main limitations of the study include its retrospective design and the relatively small sample size in the embryological outcome analysis. The results of our study should be viewed with caution as different malignancy types were included in the study groups, although their distribution between the study groups was similar. WIDER IMPLICATIONS OF THE FINDINGS: Cancer grade seems to have a negative impact on the fertility preservation outcome and the ovarian stimulation response. STUDY FUNDING/COMPETING INTEREST(S): Authors have not received any funding to support this study. There are no conflicts of interest to declare.

Complicated Clinical Course and Poor Reproductive Outcomes of Women with Tubo-Ovarian Abscess after Fertility Treatments.

STUDY OBJECTIVE: To assess the clinical course and surgical and fertility outcomes of patients diagnosed with tubo-ovarian abscess (TOA) after fertility treatment. DESIGN: Parallel case series over 10 consecutive years (Canadian Task Force classification II-2). SETTING: Tel Aviv Sourasky Medical Center, a tertiary university-affiliated hospital. PATIENTS: Thirty-seven women who were diagnosed with TOA after fertility treatments (in vitro fertilization and intrauterine insemination) were compared with 313 women who were diagnosed with TOA not associated with fertility treatments during the same time period. INTERVENTION: Medical records search, chart review, and phone survey were used to assess clinical course and surgical and reproductive outcomes. MEASUREMENTS AND MAIN RESULTS: Women with TOA after fertility treatments had significantly higher inflammatory markers upon admission compared with the nonfertility treatment group (mean white blood cell count, 16.1 × 1000/mm3 [standard deviation [SD], ±4.3] vs 13.8 × 1000/mm3 [SD, ±6.3], p = .001, respectively; and mean C-reactive protein, 149 mg/L [SD, ±78.3] vs 78.2 mg/L [SD, ±68.5], p = .001, respectively). In addition, TOA after fertility treatments was associated with a significantly higher surgical intervention rate and a more complicated clinical course, as evidenced by a shorter time interval from admission to surgery (2.1 days vs 3.2 days, p = .01), higher rates of antibiotic failure, higher conversion rate from laparoscopy to laparotomy (14.2% vs 3.2%, p = .005), increased perioperative complications rate (25.0% vs 3.8%, p = .0001), and a longer hospitalization stay (7.2 days vs 4.8 days, p = .01). Clinical pregnancy rate per cycle in women with TOA after fertility treatments was 9%, and 1 case of live birth was recorded. CONCLUSIONS: Our data indicate that TOA after fertility treatment has a substantial effect on the clinical course and surgical outcome. Prophylactic antibiotic treatment before ovum retrieval and deferral of embryo transfer should be considered in patients at risk of infection.