Enhancing the scope of in vitro maturation for fertility preservation: transvaginal retrieval of immature oocytes during endoscopic gynaecological procedures.

STUDY QUESTION: Could in vitro maturation (IVM) following transvaginal oocyte retrieval during gynaecological surgery (IVM-surgery) be an effective and safe strategy for fertility preservation? SUMMARY ANSWER: IVM-surgery on unstimulated ovaries is a novel option that can be considered for fertility preservation for women requiring gynaecological surgery, but more research is needed to identify appropriate patients who may benefit and to determine the cost-effectiveness of such an approach. WHAT IS KNOWN ALREADY: IVM followed by oocyte/embryo cryopreservation has been useful as a safe reproductive strategy for some infertile women. STUDY DESIGN, SIZE, DURATION: This prospective cohort study comprised 158 consecutive women with polycystic ovary syndrome (PCOS) who underwent laparoscopy or hysteroscopy for other reasons and had concomitant transvaginal oocyte retrieval followed by IVM between 2014 and 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 158 women with anovulatory PCOS who underwent IVM-surgery in our infertility centre were recruited for this study. Matured IVM oocytes obtained from these women were either freshly fertilized and subsequently frozen at the blastocyst stage (fresh oocyte group, n = 46) or the oocytes were frozen (frozen oocyte group, n = 112) for fertility preservation followed by later thawing for insemination and cleavage embryo transfer (ET) (n = 33). The following outcomes were then evaluated: embryological data, clinical pregnancy rate, live birth rate (LBR), neonatal outcomes, post-operative complications and post-operative ovarian function. MAIN RESULTS AND THE ROLE OF CHANCE: Among all the women who underwent IVM-surgery, the clinical pregnancy rate and LBR per initiated IVM cycle were 9.5% (15/158) and 6.9% (11/158), respectively. Women (40.6%, 20/33) who underwent the procedure with frozen-thawed oocytes (oocyte survival rate, 83.0%) obtained a high quality of cleaved embryos. In the fresh oocyte group, the clinical pregnancy rate and LBR per ET cycle were 69.2 and 53.8%, respectively. In the frozen oocyte group, the clinical pregnancy rate and LBR per ET cycle were 28.6 and 19.1%, respectively. No adverse neonatal outcomes were recorded. IVM-surgery was not associated with post-operative complications, a longer hospital stay, or impaired ovarian function. LIMITATIONS, REASONS FOR CAUTION: Because of the small sample size and the low utilization rate and cost-effectiveness per retrieval, the present findings should be interpreted with caution, and further studies are needed for the long-term follow-up of live births. WIDER IMPLICATIONS OF THE FINDINGS: This strategy can also help patients with normal ovulation to obtain available oocytes and embryos for cryopreservation and subsequent use. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the Joint Research Fund for Overseas Natural Science of China (No. 31429004), the National Key Research and Development Program of China (No. 2017YFC1002000, 2017YFC1001504, 2016YFC1000302), the Ministry of Science and Technology of China Grants (No. 2014CB943203), the Chinese Society of Reproductive Medicine Fund (No. 16020400656) and the National Natural Science Foundation of China (No. 81300456). All the authors have nothing to disclose in terms of conflicts of interest. TRIAL REGISTRATION NUMBER: chictr-ONC-17011861.

Combined estrogen-progestin pill is a safe and effective option for endometrial hyperplasia without atypia: a three-year single center experience.

OBJECTIVE: To evaluate the effectiveness of oral contraceptive pill (OCP) as therapy for endometrial hyperplasia (EH) without atypia in reproductive-aged women compared with oral progestin. METHODS: A retrospective cohort study was carried out in our reproductive center. Consecutive patients diagnosed with infertility and non-atypical EH identified through electronic database who met inclusion criteria (n=309). Patients were assigned to two treatment groups: OCP (n=216) and oral progestin (n=93); clinical and reproductive outcomes were recorded. RESULTS: Reversal of EH to normal endometrium, clinical pregnancy, live birth and miscarriage rate. Women in OCP group were younger, had higher prevalence of Polycystic Ovary Syndrome and other uterine pathology and longer duration of infertility than women in progestin group. Reversal of EH was observed in 93.52% women on OCP and in 86.02% women on progestin (p=0.032; adjusted odds ratio [aOR]= 2.35; 95% confidence interval [CI]=1.06-5.21) after the initial course of treatment for 2 to 6 months. Cyclic OCP (n=184) resulted in better response to treatment compared to continuous OCP (n=32) (95.11% vs. 84.38%; p=0.039; aOR =3.60; 95% CI =1.12-11.55). Clinical pregnancy rate in OCP group was marginally higher than progestin group (87/208, 41.83% vs. 27/90, 30.00%; p=0.054). Miscarriage (25.29% vs. 29.63%; p=0.654) and live birth rate (31.25% vs. 21.11%; p=0.074) were comparable between the groups. CONCLUSION: For the first time we demonstrate that OCP is an effective therapy for non-atypical EH and is associated with higher remission rate compared with oral progestin. Reproductive outcomes are reassuring and comparable between the two groups.

Plasma miRNAs Display Limited Potential as Diagnostic Tools for Endometriosis.

CONTEXT: Despite extensive searches for novel noninvasive diagnostics, laparoscopy remains the reference test for endometriosis. Circulating miRNAs are purported endometriosis biomarkers; however, the miRNA species and their diagnostic accuracy differ between studies and have not been validated in independent cohorts. OBJECTIVE: Identify endometriosis-specific plasma miRNAs and determine their diagnostic test accuracy. SETTING: Two university-based, public hospitals and a private gynecology practice in Australia. DESIGN AND PARTICIPANTS: Four phases: (i) Explorative phase. Plasma miRNA menstrual cycle fluctuations were evaluated in women with endometriosis and asymptomatic controls (n = 16). (ii) Biomarker discovery. Endometriosis-specific plasma miRNAs were identified in (a) women with endometriosis and asymptomatic controls (n = 16) and (b) women with and without surgically defined endometriosis (n = 20). (iii) Biomarker selection. Plasma miRNAs with the best diagnostic potential for endometriosis were selected in a surgically defined selection cohort (n = 78). (iv) Biomarker validation. The diagnostic test accuracy of these miRNAs was calculated in an independent, surgically defined validation cohort (n = 119). RESULTS: Forty-nine miRNAs were differentially expressed in women with endometriosis. Nine maintained dysregulation in the selection cohort, but only three (miR-155, miR574-3p and miR139-3p) did so in the validation cohort. Combined, these three miRNAs demonstrated a sensitivity and specificity of 83% and 51%, respectively. CONCLUSION: Plasma miRNAs demonstrated modest sensitivity and specificity as diagnostic tests or triage tools for endometriosis. Other groups' findings were not replicated and accorded poorly with our results. Circulating miRNAs demonstrate diagnostic potential, but stringent, standardized methodological approaches are required for the development of a clinically applicable tool.

Reproductive outcomes in women with unicornuate uterus undergoing in vitro fertilization: a nested case-control retrospective study.

BACKGROUND: Unicornuate uterus, a congenital uterine malformation resulting from unilateral maldevelopment of Mullerian duct, is more prevalent in women with infertility. Owing to relative rarity of the condition, the evidence on the associated reproductive outcomes is derived from small heterogeneous studies that report different clinical endpoints and often do not account for the anatomical variations of unicornuate uterus. The aim of this study was to evaluate the embryological and clinical outcomes following IVF-ICSI treatment in women with unicornuate uterus without rudimentary functional cavity (ESHRE-ESGE class IVb). METHODS: Retrospective nested case-control study comprised 342 women with unicornuate uterus and 1026 matched controls who underwent IVF-ICSI cycles between October 2012 and October 2016. Cumulative live birth rate upon one complete IVF cycle, including transfers of all resulting embryos was considered as a primary outcome measure. RESULTS: Baseline characteristics were comparable between the unicornuate uterus and control groups except for higher rate of primary infertility in unicornuate uterus. Ovarian response to stimulation did not differ between the groups. Transfer of day-3 embryos in fresh cycle resulted in lower clinical pregnancy rate (35.9% vs. 43.9%, p = 0.028) and live-birth rate (26.9% vs. 35.2%, p = 0.017) per transfer, but the difference was not observed when either cleavage frozen-thaw embryos or blastocysts were transferred. Implantation rate was lower and miscarriage rate was higher in women with unicornuate uterus but the difference between the groups did not reach statistical significance. Transfer of cleavage embryos resulted in significantly higher miscarriage rate and lower live-birth rate in fresh versus frozen-thaw cycles in each group, whereas fresh and frozen-thaw blastocyst embryos had comparable outcomes. Upon completion of one IVF-ICSI cycle, the cumulative pregnancy rate (53.1% vs. 65.7, p < 0.001) and cumulative live birth rate (42.4% vs. 54.6%, p < 0.001) were significantly lower in women with unicornuate uterus compared to those in women with normal uterus. Cumulative outcomes were superior when embryos were cultured to blastocyst stage. CONCLUSIONS: Women with unicornuate uterus have lower clinical pregnancy and live birth rate after IVF-ICSI treatment compared to women with normal uterus. The treatment outcomes are improved with blastocyst culture, which warrants evaluation in prospective setting.

Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial.

BACKGROUND: Management of women with reduced ovarian reserve or poor ovarian response (POR) to stimulation is one of the major challenges in reproductive medicine. The primary causes of POR remain elusive and oxidative stress was proposed as one of the important contributors. It has been suggested that focus on the specific subpopulations within heterogeneous group of poor responders could assist in evaluating optimal management strategies for these patients. This study investigated the effect of anti-oxidant treatment with coenzyme Q10 (CoQ10) on ovarian response and embryo quality in young low-prognosis patients with POR. METHODS: This prospective, randomized controlled study included 186 consecutive patients with POR stratified according to the POSEIDON classification group 3 (age < 35, poor ovarian reserve parameters). The participants were randomized to the CoQ10 pre-treatment for 60 days preceding IVF-ICSI cycle or no pre-treatment. The number of high quality embryos was a primary outcome measure. RESULTS: A total of 169 participants were evaluated (76 treated with CoQ10 and 93 controls); 17 women were excluded due to low compliance with CoQ10 administration. The baseline demographic and clinical characteristics were comparable between the groups. CoQ10 pretreatment resulted in significantly lower gonadotrophin requirements and higher peak E2 levels. Women in CoQ10 group had increased number of retrieved oocytes (4, IQR 2-5), higher fertilization rate (67.49%) and more high-quality embryos (1, IQR 0-2); p < 0.05. Significantly less women treated with CoQ10 had cancelled embryo transfer because of poor embryo development than controls (8.33% vs. 22.89%, p = 0.04) and more women from treatment group had available cryopreserved embryos (18.42% vs. 4.3%, p = 0.012). The clinical pregnancy and live birth rates per embryo transfer and per one complete stimulation cycle tended to be higher in CoQ10 group but did not achieve statistical significance. CONCLUSION: Pretreatment with CoQ10 improves ovarian response to stimulation and embryological parameters in young women with poor ovarian reserve in IVF-ICSI cycles. Further work is required to determine whether there is an effect on clinical treatment endpoints.

Tissue and circulating microRNA influence reproductive function in endometrial disease.

microRNA (miRNA) have emerged as important epigenetic modulators of gene expression in diverse pathological and physiological processes. In the endometrium, miRNA appear to have a role in the dynamic changes associated with the menstrual cycle, in implantation and in the pathophysiology associated with reproductive disorders such as recurrent miscarriage and endometriosis. This review explores the role of miRNA in endometrial physiology and endometrial disorders of reproduction and also raises the prospect that circulating miRNA may modulate endometrial function or reflect disordered endometrial activity. The clinical potential to use miRNA in diagnostic tests of endometrial function or in the treatment of endometrial disorders will also be discussed.

Obesity and reproductive dysfunction in women.

Overweight and obesity are significant and increasing health problems associated with increased risks of morbidity, quality of life, and metabolic and reproductive health consequences. In women, being overweight or obese is associated with impaired fertility and decreased chance of conception both in natural and assisted reproductive technology births. During pregnancy, overweight and obesity are associated with increased risk of adverse maternal and infant health outcomes. Attention to weight loss before conception may improve fertility and maternal and infant health outcomes during pregnancy.

Ehlers-Danlos syndrome: insights on obstetric aspects.

UNLABELLED: Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperelasticity, tissue fragility, easy bruising, and poor healing of wounds. The clinical manifestations vary depending on the type of disease. The syndrome may be associated with a number of pregnancy and peripartum complications. Because of the multiorgan involvement and varied presentation of this disease, no uniform or routine obstetric and anesthetic recommendations can be made for the perinatal care of these patients. We present a review of the literature on EDS with emphasis on the obstetric, anesthetic, and perinatal consequences. We also report our experience with this syndrome: an uneventful term vaginal delivery in a 32-year-old woman diagnosed with hypermobility type of EDS. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall the potentially severe nature of Ehlers-Danlos Syndrome (EDS) in both pregnant and nonpregnant patients, summarize the wide range of signs and symptoms and its genetic inheritance, and explain the difficulty in recommending obstetric and anesthesia procedures to avoid complications.

Maternal complications associated with multiple cesarean deliveries.

OBJECTIVE: The claim that a planned repeat cesarean delivery is safer than a trial of labor after cesarean may not be applicable to women who desire larger families. The aim of this study was to assess maternal complications after multiple cesarean deliveries. METHODS: The records of women who underwent two or more planned cesarean deliveries between 2000 and 2005 were reviewed. We compared maternal complications occurring in 277 women after three or more cesarean deliveries (multiple-cesarean group) with those occurring in 491 women after second cesarean delivery (second-cesarean group). RESULTS: Excessive blood loss (7.9% versus 3.3%; P < .005), difficult delivery of the neonate (5.1% versus 0.2%; P < .001), and dense adhesions (46.1% versus 25.6%; P < .001) were significantly more common in the multiple-cesarean group. Placenta accreta (1.4%) and hysterectomy (1.1%) were more common, but not significantly so, in the multiple-cesarean group. The proportion of women having any major complication was higher in the multiple-cesarean group, 8.7% versus 4.3% (P = .013), and increased with the delivery index number: 4.3%, 7.5%, and 12.5% for second, third, and fourth or more cesarean delivery, respectively (P for trend = .004). CONCLUSION: Multiple cesarean deliveries are associated with more difficult surgery and increased blood loss compared with a second planned cesarean delivery. The risk of major complications increases with cesarean delivery number. LEVEL OF EVIDENCE: II-2.

Results of a well-defined protocol for a trial of labor after prior cesarean delivery.

OBJECTIVE: It has been claimed that a trial of labor after cesarean carries higher maternal and fetal risks than planned cesarean delivery. Because the management of such patients in our department differs from that described in some studies, and is perhaps more cautious, we hypothesized that the outcome may be better. METHODS: We identified women with 1 previous low uterine segment cesarean who had delivered a cephalic singleton infant at gestational age 34 weeks or more from January 2000 through May 2005. Our policy is to encourage such women to undergo a trial of labor unless cesarean delivery is indicated. Unless otherwise indicated, our policy is to wait for spontaneous labor. We do not use prostaglandins, and recommend cesarean delivery if the cervix is unripe.(Bishop score < 6). We compared the outcome between women who underwent a trial of labor and women who underwent planned cesarean delivery. RESULTS: A trial of labor was attempted by 841 women (80% successful), and 467 underwent planned cesarean delivery. Uterine rupture was observed in 1 woman 18 hours after vaginal delivery. There was no difference in major or minor maternal morbidity. There was no serious neonatal morbidity. Among the planned cesarean patients, hospital stay was longer, and there were more admissions to the neonatal intensive care unit. CONCLUSION: With our well-defined protocol, a trial of labor after cesarean seems to be as safe for the mother and infant as planned cesarean delivery, and the hospital stay is shorter. LEVEL OF EVIDENCE: II-2.