Fertility preservation parameters in patients with haematologic malignancy: a systematic review and meta-analysis.

Patients with haematologic malignancies represent one of the most common groups referred for fertility preservation before gonadotoxic oncological treatment. The aim of this systematic review and meta-analysis was to evaluate the effect of haematologic cancer on ovarian reserve and response to ovarian stimulation compared with healthy controls. A total of eight observative studies were included in the final quantitative analysis. Despite a younger age (mean difference -4.17, 95% CI -6.20 to -2.14; P < 0.0001), patients with haematologic malignancy had lower serum anti-Müllerian hormone levels compared with the control group (MD -1.04, 95% CI -1.80 to -0.29; P = 0.007). The marginally higher total recombinant FSH dose (MD 632.32, 95% CI -187.60 to 1452.24; P = 0.13) and significantly lower peak oestradiol serum level (MD -994.05, 95% CI -1962.09 to -26.02; P = 0.04) were demonstrated in the study group compared with the healthy controls. A similar number of retrieved oocytes were achieved in both groups (MD 0.20, 95% CI -0.80 to 1.20; P = 0.69). In conclusion, haematologic malignancies may detrimentally affect ovarian function manifesting in decreased AMH serum levels despite a younger age compared with healthy controls. This effect can be overcome by the application of relevant IVF protocols and stimulation doses to achieve an adequate oocyte yield.

Fertility preservation for women with ovarian endometriosis: results from a retrospective cohort study.

RESEARCH QUESTION: What is the outcome of fertility-preservation treatments in women with endometrioma, especially those with endometrioma larger than 4 cm? DESIGN: Retrospective cohort study. Women with definitive diagnosis of ovarian endometriosis (by histology or ultrasound), who underwent fertility-preservation treatment in two IVF units between 2016 and 2021, were included. As some women cryopreserved oocytes and other embryos, the primary outcome was the number of metaphase II (MII) oocytes retrieved. RESULTS: Seventy-one women with ovarian endometriosis (OMA) underwent 138 fertility-preservation cycles. The median age of patients was 31 years. Forty out of 71 (56%) women underwent at least one surgery for OMA before fertility-preservation treatment. Multivariate analysis of each patient's first cycle was used. Women who underwent OMA surgery before fertility-preservation treatment had a 51.7% reduction (95% CI 26.1 to 68.5, P = 0.001) in the number of MII oocytes compared with women with OMA who did not undergo surgery. Among a subgroup who did not undergo surgery, those with an endometrioma larger than 4 cm had similar anti-Müllerian hormone concentration (2.6 ng/ml versus 2.1 ng/ml), number of oocytes retrieved (9 versus 9) and number of MII oocytes (7.6 versus seven 7) compared with women with an endometrioma of 4 cm or less. CONCLUSIONS: Discussing fertility-preservation treatment options with patients with OMA is recommended, especially if surgery is planned.

Female fragile X premutation carriers are at increased risk for metabolic syndrome from early adulthood.

BACKGROUND AND AIMS: Women with primary ovarian insufficiency exhibit an unfavorable cardiovascular risk profile. A common cause for primary ovarian insufficiency is fragile X premutation (FXPC), and data on the cardiovascular risk factors in women with FXPC are scarce. We aimed to assess the prevalences of abnormal metabolic components among FXPC. METHODS AND RESULTS: Clinical, anthropometric and laboratory data were collected from 71 women with FXPC and compared to 78 women referred for counseling in an in-vitro fertilization clinic (control group). The mean ± SD ages of the FXPC and control groups were 33.5 ± 5.6 and 36.2 ± 5.3 years, respectively (p = 0.003). In a logistic regression analysis, the FXPC group had increased risks for hyperglycemia, hypertriglyceridemia, central obesity and low high-density lipoprotein cholesterol, of 21.8-fold (95% CI 2.7-175, p = 0.004), 6.9-fold (95% CI 2.5-18.7, p < 0.0001), 3.1-fold (95% CI 1.4-6.9, p = 0.005) and 2.4-fold (95% CI 1.1-5.2, p = 0.03), compared to the control group. The FXPC group had 2.7-fold higher prevalence of two abnormal metabolic components; 19% met the full criteria of MetS, compared to 3% of the control group. Neither CGG repeats nor ovarian reserve markers were associated with metabolic risk. CONCLUSIONS: Carriers of fragile X premutation are at increased metabolic risk from early adulthood; waist circumference, glucose and lipid levels are particularly elevated. We recommend metabolic screening for all women with FMR1 premutation, to enable early interventions for prevention of long-term cardiovascular comorbidities.

Ethnicity has a multiplex impact upon the risk of a full mutation expansion among female heterozygotes for FMR1 premutation.

PURPOSE: To evaluate whether ethnicity affects the risk of full mutation expansion among females heterozygous for FMR1 premutation. METHODS: Women who carry the FMR1 premutation alelle of Jewish origin who underwent fragile X prenatal diagnosis between 2011 and 2018 in two medical centers in Israel were included. The heterozygote women and fetuses were analyzed for the number of CGG repeats and AGG interruptions. RESULTS: Seven hundred sixty-six subjects were included. Parental ethnicity was fully concordant in 592 cases (Jewish, Ashkenazi, and non-Ashkenazi). Ashkenazi compared with non-Ashkenazi heterozygotes have a significantly higher mean number of CGG repeats (68 ± 8.7, 64 ± 6.4 respectively, P = 0.03) and a lower mean number of AGG interruptions (0.89 ± 0.83, 1.60 ± 1.18 respectively, p = 0.0001). Overall, 56/198 (28.2%) fetuses of Ashkenazi heterozygotes had an expansion to a full mutation compared with 6/98 among the non-Ashkenazi (6.1%) (p = 0.001). Multivariate analysis demonstrated that, in addition to CGG repeats and AGG interruptions (which contributed 68.3% of variance), ethnicity is an independent risk factor for a full mutation expansion (odds ratio [OR] = 2.04, p < 0.001) and accounted for 9% of the variation of a full mutation expansion. CONCLUSION: Apart from significant differences regarding the number of CGG repeats and AGG interruptions between Ashkenazi and non-Ashkenazi heterozygotes, ethnicity independently affects the risk of a full mutation.

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.

Preimplantation genetic diagnosis versus prenatal diagnosis-decision-making among pregnant FMR1 premutation carriers.

PURPOSE: To detect which factors influence decision-making among pregnant FMR1 premutation carriers regarding the preferred mode of genetic diagnosis: IVF-PGT-M (in vitro fertilization with preimplantation genetic testing for monogenic gene diseases), or CVS (chorionic villus sampling), or AC (amniocentesis) after spontaneous conception. METHODS: In Israel FMR1 premutation preconception genetic screening is offered, free of charge, to every woman in her reproductive years. FMR1 premutation carriers with ≥ 70 CGG repeats, or a history of FXS offspring, are offered IVF-PGT-M. This is a historical cohort study including all pregnant FMR1 premutation carriers who underwent prenatal diagnosis between the years 2011 and 2016 at a tertiary medical center. Data were collected from electronic charts and through phone interviews. RESULTS: One hundred seventy-five women with high-risk pregnancies who were offered IVF-PGT-M were evaluated. In 37 pregnancies (21%), the women decided to undergo IVF-PGT-M. Using the generalized estimating equations (GEE) statistical method including seven parameters, we found that previous termination of pregnancy due to FXS and advanced woman's age were significantly associated with making the decision to undergo IVF-PGT-M. Previously failed IVF was the most significant parameter in a woman's decision not to undergo IVF-PGT-M. CONCLUSION: The most dominant factor affecting the decision of FMR1 premutation carriers to choose spontaneous conception with prenatal diagnosis versus IVF-PGT-M is a previous experience of failed IVF treatments. Women whose IVF treatments failed in the past tended to try to conceive naturally and later, during the course of the pregnancy, perform CVS or AC. Conversely, women who previously experienced a termination of pregnancy (TOP) due to an affected fetus, and older women, preferred to undergo IVF-PGT-M procedures.

[FROM GENETICS OF FRAGILE X SYNDROME TO DEVELOPMENT OF TARGETED AND PERSONALIZED DRUG THERAPY].

INTRODUCTION: At the end of the last century Fragile X syndrome was identified, and the main syndrome characteristics were discovered. The syndrome is caused from a flaw in the number of nucleotide repeats that encodes for a regulatory protein which is critical for neural connectivity and normal brain development. The syndrome is characterized by neurodevelopmental and intellectual disabilities, autism spectrum features and other clinical features associated with the same gene aberration. The number of trinucleotide repeats have a direct effect on the outcome and the need for genetic counseling. We advocate performing genetic tests for every child with developmental delay, learning disabilities, autism spectrum disorders and especially, intellectual impairment. It is also advisable to check the number of nucleotide repeats of the gene, in every woman suffering from infertility or early menopause. In addition, genetic testing should be performed on older adults manifesting early symptoms of Parkinson's disease, balance instability, tremor or cognitive dysfunction with unknown etiology. Due to the tremendous progress in understanding the biological mechanisms of the syndrome, new molecules/drugs have been proposed and are tested, in order to find a way to bypass the defect mechanism underlying the disorder. We will review the most commonly used drugs in the treatment of Fragile X syndrome and many medications that are currently under investigation as a more targeted treatment.

[FMR1 PREMUTATION CARRIERS - ARE THEY REALLY ASYMPTOMATIC?]

INTRODUCTION: Fragile X Syndrome (FXS), the most common form of inherited mental retardation, is caused by a trinucleotide repeat expansion (CGG) in the 5'-untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene located at Xq27.3. Patients with fragile X -related mental retardation, carry the full mutation CGG-repeat expansions (>200 CGG repeats), which are generally accompanied by hypermethylation of the promoter region, with the consequent transcriptional silencing of the FMR1 gene and absence of the encoded FMR1 protein (FMRP). Expansion of the CGG triplet number above the normal range (n=5-54) towards the so-called premutation status (n=55-199) is associated with increased risk for Fragile X-Associated Premature Ovarian Insufficiency (FXPOI) in females and Fragile X-Associated Tremor/ Ataxia Syndrome (FXTAS) predominantly in males. In addition, premutation women carriers are at increased risk for learning disabilities, as well as psychologic, endocrine, autoimmune and metabolic disorders. The observation that premutation carriers, both males and females, have increased FMR1 transcript levels, led researchers to suggest a similar molecular pathogenesis in both FXPOI and FXTAS. Two models have been proposed as the culprits of FXTAS and FXPOI: The toxic RNA gain-of-function model and the Repeat Associated Non-AUG initiated (RAN) translation protein toxicity model. The Fragile X Multidisciplinary Center in Sheba Medical Center, at Tel Hashomer includes a team of geneticists, fertility specialists, endocrinologists, psychologists and neurologists who work together in order to provide early detection of FMR1 premutation carriers and offer FMR1 premutation carriers and their families adequate multidisciplinary medical consultation, follow-up and care.

Fragile X Premutation Carrier Epidemiology and Symptomatology in Israel-Results from a Tertiary Child Developmental Center.

Fragile X syndrome (FXS) is the most prevalent known genetically inherited cause for autism and intellectual disability. Premutation state can cause several clinical disorders as well. We aimed to perform a nesting approach to acquire data with regard to first degree relatives of index fragile X cases at the largest child development center in Israel in order to map characteristics of Israeli FXS permutation women carriers. Seventy-nine women were referred due to a related fragile X syndrome patient, mainly an offspring or sibling. General information regarding demographics, ethnicity, and associated medical conditions were collected using interviews and structured questionnaires. Thirteen (17 %) of the women who were referred as "carrier" were proven to be actually full mutation. The mean years of education were 14 (±1.51, range 12-17). Twenty-one women (27 %) originated from Tunisia (mainly from the island of Djerba). Ten women (13 %) reported delivery of their affected offspring beyond 41 gestational weeks. Twenty-two percent of women with premutation reported symptoms consistent with learning difficulties, mainly dyscalculia, and 14 % reported ADHD symptoms. Awareness about clinical disorders of the carriers was existent only in 25 % of the patients. Increased awareness and knowledge dissemination concerning premutation symptomatology and associated medical conditions are warranted. We suggest a national registry to be installed in different countries in order to identify fragile X premutation carriers at increased risk for various medical complications.

FMR6 may play a role in the pathogenesis of fragile X-associated premature ovarian insufficiency.

The aim of this study was to evaluate whether long noncoding RNA accumulation play a role in the pathophysiology of fragile X-associated premature ovarian insufficiency (FXPOI). The study population consisted of 22 consecutive fragile X mental retardation 1 (FMR1) premutation carriers (CGGn 55-199 repeats) undergoing in vitro fertilization and pre-implantation genetic diagnosis (IVF-PGD) treatment. The control group consists of 11 patients, with <55 CGG repeats, undergoing IVF-ICSI for male factor infertility, matched by age, treated in the same period. After oocyte retrieval, granulosa cells from follicular fluid were washed and stored at -80 °C. RNA was transcribed to generate cDNA and the RNA levels were measured using RT-PCR. Transcripts levels in granulosa cells of long noncoding RNA's FMR4 and FMR6 were measured. In FMR1 premutation carriers there was a significant nonlinear association between the number of CGG repeats and the levels of FMR6 (p = 0.03), but not FMR4. The highest level of FMR6 was seen in women with mid-size CGG repeats (80-120). In addition, a significant negative linear correlation was observed between the number of oocytes retrieved and the RNA levels in granulosa cells of FMR6 (r = -0.53, p = 0.01) but not FMR4. Our study supports previous findings suggesting RNA toxic gain-of-function as one of the possible pathophysiologic mechanisms underlying FXPOI.

Reproductive Outcome Is Favorable After Laparoscopic Resection of Bladder Endometriosis.

STUDY OBJECTIVE: To assess the reproductive outcome (spontaneous and assisted conception rates) in women who underwent laparoscopic resection of bladder endometriosis. DESIGN: This was a retrospective, observational study analyzing prospectively recorded data (Canadian Task Force classification II-2). SETTING: A tertiary referral center. PATIENTS: Over a 9-year period, we identified 69 consecutive women with symptomatic pelvic endometriosis who underwent laparoscopic resection of bladder endometriosis at our center. INTERVENTIONS: Group A patients (n = 21) had full-thickness endometriotic invasion of the bladder and underwent laparoscopic partial cystectomy. Group B (n = 48) patients had partial endometriotic bladder penetration and underwent partial-thickness excision of the detrusor muscle. Most patients (over 70%) had additional, nonbladder endometriotic lesions, which were also removed during surgery. MEASUREMENTS AND MAIN RESULTS: Fertility outcomes were analyzed in patients who wished to conceive (n = 42), and improvements in symptoms were assessed for all patients. The minimum follow-up after surgery was 36 months. Of the 42 patients who wished to conceive, 35 patients (83.3%) conceived: 16 patients spontaneously and 18 patients after IVF treatment. No difference was observed in fertility outcome between group A (partial cystectomy) and group B (partial-thickness excision of the detrusor muscle). For all patients, long-term follow-up revealed that 80% of the patients (55 patients) had no urinary/endometrial symptoms after surgery. CONCLUSION: Pregnancy rates after laparoscopic surgery for bladder endometriosis by either partial cystectomy or deep excision of the detrusor muscle are favorable, both for spontaneous pregnancy and conception after IVF treatment. Additionally, urinary symptoms were improved for the majority of patients. Based on our findings, it seems warranted to offer laparoscopic surgical management to symptomatic infertile patients diagnosed with bladder endometriosis, even after IVF failure.

Pregnancy outcome of early multifetal pregnancy reduction: triplets to twins versus triplets to singletons.

Multifetal pregnancy reduction (MPR) of triplets to twins results in improved pregnancy outcomes compared with triplet gestations managed expectantly. Perinatal outcomes of early transvaginal MPR from triplets to twins were compared with reduction from triplets to singletons. Seventy-four trichorionic triplet pregnancies that underwent early transvaginal MPR at 6-8 weeks gestation were included. Cases were divided into two groups according to the initial procedure: reduction to twin (n = 55) or to singleton (n = 19) gestations. Infants from triplet pregnancies reduced to twins were delivered earlier (36.6 versus 37.9 weeks; P = 0.04) and had lower mean birth weights (2364 g versus 2748 g; P = 0.02) compared with those from triplets reduced to singleton gestations. The rates of pregnancy loss before 24 weeks (3.6% versus 5.3%), as well as of preterm delivery before 32 and 34 weeks of gestation (0% versus 5.3% and 7.3% versus 5.3%, respectively) were similar between the twin and singleton pregnancies. No significant difference was found in the prevalence of gestational diabetes (15.1% versus 5.6%) or gestational hypertension (24.5% versus 16.7%) between the groups. Selective reduction of triplet pregnancies to singleton rather than twin gestations is associated with improved outcomes.

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.

Reactive oxygen species in follicular fluid may serve as biochemical markers to determine ovarian aging and follicular metabolic age.

INTRODUCTION: The aim of this study was to evaluate the role of oxidative stress in the process of ovarian aging. METHODS: Follicular fluid (FF) from two randomly selected sibling follicles was collected from women undergoing in-vitro fertilization and tested for hydrogen peroxide (H(2)O(2)) levels. RESULTS: Group A consists of seven women with whom each of the two sibling separate follicle yielded an oocyte that was later discordantly developed to a low- and top-quality embryo. Group B consists of 13 patients in whom one of the sibling follicle yielded an oocyte while the other did not (empty follicle). High-quality embryos were derived from follicles with lower H(2)O(2) levels compared to follicles from which poor-quality embryos developed (1.004 units ± 0.260 versus 1.145 units ± 0.236, p < 0.02). H(2)O(2) levels were significantly higher (0.951 units ± 0.233 versus 0.623 units ± 0.309, p < 0.001) in sibling follicles containing oocyte compared to empty follicles. CONCLUSION: During the process of ovarian ageing, there might be a gradual increase in H(2)O(2) level in the follicle. Finally, when the follicle ages and becomes empty of oocyte H(2)O(2) levels drops significantly. Therefore, H(2)O(2) levels in FF may serve as a possible marker to determine ovarian aging and follicular metabolic age.

Cryopreservation of day 2-3 embryos by vitrification yields better outcome than slow freezing.

OBJECTIVE: To compare the outcome of vitrification versus slow freezing cryopreservation for cleavage stage day 2-3 embryos. DESIGN: A retrospective observational study. SETTING: All thawed embryos assisted reproduction cycles between January 2010 and December 2012 at a single IVF laboratory of a Tertiary Medical Center. PATIENTS: Five hundred and thirty-nine cycles of day 2-3 thawed embryos. INTERVENTIONS: In 327 of the thawed cycles, the embryos were vitrified and in 212 of the cycles the embryos were derived from slow freezing embryos. MAIN OUTCOMES MEASURE: Embryo survival rate, blastomere surviving rate and pregnancy rate. RESULTS: Embryo survival rate was significantly higher after vitrification compared with slow freezing (81.6%, 647/793 versus 70.0%, 393/562 embryos, p < 0.0001). The clinical pregnancy rate per ET was significantly higher following vitrification compared to slow freezing, 20.0%, 63/314 versus 11.9%, 23/193, respectively (p = 0.02). CONCLUSIONS: Vitrification of day 2-3 cleavage stage embryos yields better cycle outcome in all the parameters compared to slow freezing.

Pelvic inflammatory disease in women with endometriosis is more severe than in those without.

AIMS: To determine the incidence and severity of acute pelvic inflammatory disease (PID) or tubo-ovarian abscess (TOA) in hospitalised women with and without a history of endometriosis. METHODS: Retrospective analysis of hospital records retrieved for all women hospitalised with PID or TOA between January 2008 and December 2011 in a tertiary referral centre. Women were compared with regard to a history of endometriosis for demographic, clinical and fertility data. RESULTS: 26 (15%) of the 174 women hospitalised due to PID or TOA were excluded because of age older than 45 years, leaving 148 for analysis. The mean age was 35.7 ± 9.3 years and mean duration of hospitalisation was 5.9 ± 3.7 days. The women were divided into two groups: Group 1 with endometriosis (n = 21) and Group 2 without endometriosis (n = 127). Women in Group 1 as compared with Group 2 were significantly more likely to have undergone a fertility procedure prior to being admitted to the hospital with PID (9/27 (45%) vs 22/121 (17%), P < 0.001); particularly in vitro fertilisation (IVF) (7/ 27 (33%) vs 12/121 (9%), P < 0.006); Women in Group 1 more frequently experienced a severe and complicated course involving longer duration of hospitalisation (8.8 ± 4.7 vs 4.4 ± 2.3 days, P < 0.0001) and antibiotic treatment failure (10/27 (48%) vs 8/121 (6%), P < 0.0001). CONCLUSIONS: Pelvic inflammatory disease in women with endometriosis is more severe and refractory to antibiotic treatment, often requiring surgical intervention. It is likely that endometriosis is a risk factor for the development of severe PID, particularly after IVF treatment.

Endometrioma increases the risk of antibiotic treatment failure and surgical intervention in patients with pelvic inflammatory disease.

OBJECTIVE: To evaluate the outcome of pelvic inflammatory disease (PID) in patients with endometriosis with and without ovarian endometrioma. DESIGN: A retrospective cohort study. SETTING: A single university-affiliated tertiary center. PATIENT(S): A total of 116 patients with endometriosis hospitalized because of PID between the years 2011-2021. Fifty-nine patients with an ovarian endometrioma component were compared with 57 patients with endometriosis without endometrioma. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was severe PID defined as the need for surgical intervention or drainage. Secondary outcomes included tubo-ovarian abscess, number of hospitalization days, a positive cervical bacterial culture or urine sexually trasmitted disease polymerase chain reaction (STD PCR) test, and readmission because of partially treated or relapsing PID. RESULT(S): PID in patients with endometrioma was found less likely to respond to antibiotic treatment with increased risk for surgical intervention or drainage compared with endometriosis patients without endometrioma (adjusted odds ratio, 3.5; confidence interval, 1.25-9.87). On admission, patients with endometrioma were older (26.5 vs. 31.0) and less likely to have an intrauterine device (19.3% vs. 5.1%) compared with patients without endometrioma. The rate of the tubo-ovarian abscess (52.5% vs. 19.3%) was significantly higher in patients with endometrioma. Readmission rate, positive bacterial culture, and hospitalization duration were higher in the endometrioma group; however, they did not reach statistical significance. Recent oocyte retrieval and patient's age were not associated with an increased risk of severe PID. CONCLUSION(S): Endometrioma patients with PID are less likely to respond to antibiotic treatment and present a higher risk for surgical intervention.

Granulosa Cell Dysfunction Is Associated With Diminished Ovarian Response in FMR1 Premutation Carriers.

CONTEXT: FMR1 premutation (PM) carriers are at increased risk of ovarian impairment resulting in diminished ovarian response (DOR) to exogenous follicle-stimulating hormone (FSH) stimulation. Expanded CGG repeat transcript and RAN-associated protein (FMRpolyG) have been shown to accumulate in cellular aggregates and sequester proteins, thus impairing their function. Sam68 is a multifunctional RNA-binding protein highly expressed in the gonads involved in FSH receptor (FSHR) transcript maturation during FSH-dependent follicular development. OBJECTIVE: The present study examined a possible pathophysiological explanation for DOR to exogenous FSH stimulation in FMR1 PM carriers. METHODS: We used both a human granulosa cell (GC) line model and human GCs from FMR1 PM carriers to evaluate whether Sam68 is sequestered with expanded CGG repeat transcript. RESULTS: We show that Sam68 is sequestered in GCs, most likely by interaction with the expanded CGG repeat transcript. The sequestration may lead to reduced levels of free Sam68 available for FHSR precursor transcript processing, causing dysregulation of FSHR transcript maturation, and a consequent decrease in FSHR protein levels. CONCLUSION: Sam68 sequestration may underlie the diminished ovarian response to FSH stimulation in FMR1 PM carriers.

Relationship between the follicular distribution pattern of polycystic ovaries and the degree of menstrual disturbance and serum sex steroid levels.

Objective: This study aimed to examine the associations between follicular distribution pattern (FDP) in polycystic ovaries and menstrual disturbances in women with infertility. Materials and Methods: A retrospective review of patients was performed (n=73). Ultrasound images from cycle day 2-5 of a spontaneous or progestin induced menstrual cycle were reviewed. Ovaries were classified as polycystic ovarian morphology (PCOM) if they contained ≥12-follicles measuring 2-9 mm in diameter. Images of PCOM ovaries were classified as having a peripheral cystic pattern (PCP) with follicles arranged at the periphery of the ovary, or general cystic pattern (GCP) if follicles were dispersed heterogeneously throughout the ovarian stroma. Menstrual disturbance was assessed by questionnaire, and oligomenorrhea was defined as cycles >35 days in length. Results: PCP was more strongly associated with menstrual irregularity that GCP. 94% of subjects with bilateral PCP-experienced oligomenorrhea compared with 65% of women with a unilateral PCP ovary [odds ratio (OR) 9; p<0.05]. 29% of women with bilateral GCP ovaries experienced menstrual disturbances, less than bilateral PCP (OR 36; p=0.002), but similar to unilateral PCP (OR 3; p=0.07). Serum testosterone and luteinizing hormone (LH) levels were significantly correlated with the ovarian FDP. Conclusion: There is a relationship between menstrual irregularity or certain types of serum steroids and ovarian morphology. It remains unknown if morphology, testosterone or LH causes the menstrual disturbance or if they are co-initiated by an intervening factor.

A comprehensive evaluation of progestin-primed ovarian stimulation protocol in patients with or without PCOS undergoing in vitro fertilization.

Progestin-primed ovarian stimulation (PPOS) regimen was established for assisted reproduction. However, its feasibility and outcomes in polycystic ovary syndrome (PCOS) patients need further evaluation. The outcomes of infertile patients with PCOS (study group) and normal ovaries (control group with unexplained infertility and tubal factor infertility) who underwent PPOS and IVF/ICSI protocol were retrospectively studied. The baseline information, primary, and secondary outcomes of patients were collected. The dynamic changes of hormones were closely monitored. 198 PCOS patients and 374 controls were included in this study. After controlled ovarian hyperstimulation (COH), 15 oocytes were retrieved from PCOS patients on average, which was more than those from the controls (p < 0.001). The oocytes and embryos obtained from the PCOS patients exhibited better developmental potential as the number of fertilized oocytes, cleaved embryos, top-quality embryos, viable embryos, cryopreserved embryos, the rate of fertilization, and viable embryo per oocyte retrieved in PCOS patients were significantly higher than those in the controls (all p < 0.001). No significant difference between the two groups was identified regarding the primary outcome, ongoing pregnancy, and other secondary outcomes. No moderate to severe ovarian hyperstimulation syndrome (OHSS) was diagnosed in either group. With the proposed PPOS protocol, the quantity, quality, developmental potential of oocytes, and embryos obtained from PCOS patients were superior to those from controls. The protocol was efficient and safe in terms of pregnancy, obstetric, and perinatal outcomes. OHSS was effectively mitigated in the patients, with or without PCOS, who underwent COH.