Long-term pituitary downregulation before frozen embryo transfer could improve pregnancy outcomes in women with adenomyosis

Abstract

Some studies have shown that long-term gonadotropin-releasing hormone (GnRH) agonist administration before in vitro fertilization/intracytoplasmic sperm in infertile women with endometriosis or adenomyosis significantly increases the chances of pregnancy. We were interested in whether long-term GnRH agonist pretreatment could improve pregnancy outcomes in adenomyosis patients undergoing frozen embryo transfer (FET) after preparation of the endometrium with hormone replacement therapy (HRT). Totally, 339 patients with adenomyosis were included in this retrospective study, 194 received long-term GnRH agonist plus HRT (down-regulation?+?HRT) and 145 received HRT. There were no differences between the groups in characteristic such as age, body mass index, duration or cause of infertility, serum CA-125 level and basal hormone levels. On the day of progesterone administration, mean endometrial thickness and serum progesterone level were significantly greater in HRT patients. Mean score and number of embryos transferred showed no differences. In down regulation?+?HRT group, clinical pregnancy, implantation and ongoing pregnancy rates were 51.35%, 32.56% and 48.91%, respectively, significantly higher than that of HRT group (24.83%, 16.07% and 21.38%, respectively). So, we concluded that in FET, long-term GnRH agonist pretreatment significantly improved pregnancy outcomes in patients with adenomyosis.     

Semen treatment with progesterone and/or acetyl-L-carnitine does not improve sperm motility or membrane damage after cryopreservation-thawing

OBJECTIVE: To assess the effects of progesterone and acetyl-L-carnitine used before semen cryopreservation-thawing on sperm motility parameters and plasma membrane integrity. DESIGN: Prospective cohort study.Setting: Academic tertiary center. PATIENT(S): Subfertile men undergoing semen evaluation. INTERVENTION(S): Before cryopreservation, spermatozoa were incubated with water-soluble progesterone (1 and 10 microM), acetyl-L-carnitine (2.5, 5, 10, and 20 mM), or both (progesterone, 1 microM; and acetyl-L-carnitine, 5 mM). MAIN OUTCOME MEASURE(S): Postthaw change of motility parameters (computer-assisted measurements) and vitality-membrane integrity (examined with eosin-Y staining and annexin V-Cy3 binding assay). RESULT(S): There were no statistically significant differences between control samples and samples treated with progesterone and/or acetyl-L-carnitine for cryosurvival rate, motility parameters, or membrane integrity. The percentages of postthaw cells identified as live showed significantly different results with use of the eosin-Y staining and annexin V binding assay. CONCLUSION(S): Neither progesterone nor acetyl-L-carnitine seemed to prevent cryodamage assessed by motility changes or membrane integrity in human spermatozoa of subfertile men. Annexin V binding, a reflection of membrane translocation of phosphatidylserine, provided more distinct information about postfreezing membrane integrity changes than eosin-Y staining.     

Insertion of mirena after endometrial resection in patients with adenomyosis

STUDY OBJECTIVE: To evaluate the efficacy of Mirena, a levonorgestrel-releasing intrauterine device, after endometrial resection for treatment of menorrhagia caused by adenomyosis. DESIGN: Open, randomized, observational study (Canadian Task Force classification II-2). SETTING: Private hospital. PATIENTS: Ninety-five women. INTERVENTION: Endometrial resection, after which control patients received no further treatment and study patients had Mirena inserted immediately after the procedure. MEASUREMENTS AND MAIN RESULTS: The rate of amenorrhea after 1 year was significantly higher in the Mirena group. Nineteen percent of women in the control group had a second procedure to control bleeding compared with none in the Mirena group. CONCLUSION: Insertion of Mirena after endometrial resection is effective treatment for menorrhagia caused by adenomyosis and has very few adverse effects.     

Luteal phase support with progesterone does not improve pregnancy rates in patients undergoing ovarian stimulation with letrozole

Research questionDoes luteal phase support with vaginal progesterone improve clinical pregnancy rates in patients undergoing ovarian stimulation with letrozole?DesignThis was a retrospective cohort study of patients undergoing ovarian stimulation with letrozole paired with intrauterine insemination (IUI) or timed intercourse (TIC) from January 2018 to October 2021. The primary outcome of clinical pregnancy rate (CPR) was calculated for cycles with and without luteal phase progesterone support. Univariate logistic regressions were done to evaluate predictor variables for CPR. Clinically important covariates including age, body mass index, anti-Müllerian hormone concentration, diagnosis of ovulatory dysfunction and multifollicular development were included in a multivariate analysis evaluating the relationship between luteal progesterone use and odds of clinical pregnancy. Secondary outcomes including spontaneous abortion, biochemical pregnancy and ectopic pregnancy were calculated. Live birth rates were calculated for cycles in a secondary analysis.ResultsA total of 492 letrozole ovarian stimulation cycles in 273 patients were included. Of these cycles, 387 (78.7%) used vaginal progesterone for luteal support and 105 (21.3%) did not. The unadjusted CPR per cycle was 11.6% (45/387) with progesterone and 13.3% (14/105) without progesterone (P = 0.645). After adjusting for significant covariates including age, BMI, diagnosis of ovulatory dysfunction and multifollicular development, the odds for clinical pregnancy were not significantly improved in cycles with exogenous progesterone (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.48–2.75, P = 0.762). A follow-up analysis demonstrated that live birth rate was 10.7% (41/384) with and 12.5% (13/104) without luteal progesterone, respectively (P = 0.599).ConclusionsLuteal support with vaginal progesterone does not significantly improve CPR in ovarian stimulation cycles using letrozole.     

Hysteroscopic surgery does not adversely affect the long-term prognosis of women with endometrial adenocarcinoma

STUDY OBJECTIVE: To determine the effect of hysteroscopic surgery on the long-term clinical outcome of women diagnosed with endometrial cancer. DESIGN: Prospective cohort study (Canadian Task Force classification II-3). SETTING: University-affiliated teaching hospital. PATIENTS: From January 1990 through December 2005, the principal author (GAV) performed primary hysteroscopic surgery in 3401 women with abnormal uterine bleeding. Among these women, there were 16 occult and 3 known endometrial cancers. INTERVENTIONS: All women underwent hysteroscopic evaluation and partial (n = 8) or complete (n = 11) rollerball electrocoagulation and/or endomyometrial resection. After diagnosis of endometrial malignancy, women were counseled regarding their disease and management, in accordance with established clinical practice guidelines. Follow-up ranged from 1 to 14 years and was conducted by office visits and telephone interviews. MEASUREMENTS AND MAIN RESULTS: Among the 3401 women, there were 19 women with endometrial adenocarcinoma, 3 of whom were known to harbor cancer before hysteroscopic surgery. One woman refused hysterectomy and remains alive and well 5 years after total hysteroscopic endomyometrial resection. Two women wished to maintain fertility; 1 consented to hysterectomy after incomplete resection of her lesion. The other was treated with progestins. Her cancer reverted to complex hyperplasia, and she requested hysterectomy 4 years later. No residual cancer was found. After 5 years of follow-up, 1 patient died from carcinoma of the gallbladder (2 years), and 2 died at 4 years; 1 at the age of 87 years of natural causes and the other at the age of 86 years from acute renal failure unrelated to her cancer. Fourteen women remain alive and well at 5 to 14 years of follow-up. Two additional women remain alive and well at 1 and 4 years of follow-up. CONCLUSION: Resectoscopic surgery did not adversely affect the 5-year survival and the long-term prognosis in 14 women with endometrial cancer.     

Laparoscopic surgery does not increase the positive peritoneal cytology among women with endometrial carcinoma

OBJECTIVE: The purpose of our study was to find if uterine manipulation at the time of laparoscopic hysterectomy among women with endometrial carcinoma increases the incidence of malignant cells in the peritoneal washings. MATERIAL AND METHODS: We conducted a prospective study including women with clinical stage I endometrioid endometrial carcinoma undergoing laparoscopic surgery between 07/01/2000 and 07/01/2004. Surgery on all patients was conducted by the same surgeon using the same technique and instruments. Two sets of peritoneal washings were obtained, one before and one after the insertion of the Pelosi uterine manipulator. The two sets of washings were blindly reviewed by the same cytopathologist for the presence of malignant cells. Correlation was made between the two sets of washings. RESULTS: Forty-two consecutive women (age 46-90, median: 58) were enrolled in the study. The procedure was converted to laparotomy in 3 (7.6%) patients after obtaining the two sets of washings. The preoperative tumor grades were: G1: 22 (52.4%), G2: 12 (28.6%), and G3: 8 (19.0). The incidence of positive peritoneal washings was 14.3%. All patients underwent laparoscopically assisted vaginal hysterectomy with bilateral salpingo-oophorectomy, 30 patients had bilateral pelvic lymphadenectomy, and 5 patients had bilateral pelvic and para-aortic lymphadenectomy. There was perfect agreement between the two sets of washings in all patients (100%, P < .001). No patients had positive washings after the insertion of the uterine manipulator if the washings were negative before the insertion. The surgical stages were: IA: 14 (33.3%), IB: 12 (28.6%), IC: 7 (16.7%), IIA: 1 (2.4%), IIB: 1 (2.4%), IIIA: 4 (9.5%), IIIB: 1 (2.4%), IIIC: 1 (2.4%), and IV: 1 (2.4%). Twenty-nine patients received no postoperative treatment, 2 received chemotherapy, 3 received Megace, and 9 received radiation therapy. Patients were followed-up for 7-56 months (median: 28). Two patients had tumor recurrence, and one patient died secondary to her disease. Two other patients died secondary to other causes. CONCLUSIONS: We conclude that uterine manipulation at the time of laparoscopic hysterectomy does not increase the incidence of positive peritoneal cytology among women with endometrial carcinoma.     

Increased gonadotrophin stimulation does not improve IVF outcomes in patients with predicted poor ovarian reserve

Purpose

This retrospective study was carried out to evaluate whether increasing the starting dose of FSH stimulation above the standard dose of 150 IU/day in patients with low predicted ovarian reserve can improve IVF outcomes.

Method

A total of 122 women aged less than 36 years in their first cycle of IVF were identified as having likely low ovarian reserve based on a serum AMH measurement below 14 pmol/l. Thirty five women were administered the standard dose of 150 IU/day FSH, while the remaining 87 received a higher starting dose (200–300 IU/day FSH). There were no significant differences in age, BMI, antral follicle count, serum AMH, FSH or aetiology of infertility between the two dose groups.

Results

No significant improvement in oocyte and embryo yield or pregnancy rates was observed following an upward adjustment of FSH starting dose. While increasing the dose of FSH above 150 IU/day did not produce any adverse events such as OHSS, it did consume an extra 1,100 IU of FSH per IVF cycle.

Conclusion

The upward FSH dose adjustment in anticipation of low ovarian reserve can not be advocated as it is both expensive and of no proven clinical value.     

Postoperative reproductive outcomes in women with ovarian pregnancy: A retrospective analysis

ObjectiveThe reproductive outcomes of ovarian pregnancy are currently unknown. Therefore, the objective of our study was to report the pregnancy outcomes of women with laparoscopically treated ovarian pregnancy.Materials and methodsIn this retrospective case analysis, unpublished cases of ovarian pregnancy between 2009 and 2016 were reviewed. Women were followed up for 3 years to obtain subsequent pregnancy data.ResultsA total of 21 women who intended to become pregnant were included in this study. Predisposing risk factors for ovarian pregnancy including previous pelvic surgery (23.81%), presentation of pelvic endometriosis (23.81%), and prior intrauterine device insertion (9.52%) were identified. The major symptom at presentation was abdominal pain (85.71%), and no preoperative sonographic diagnosis of ovarian pregnancy was identified. Laparoscopic wedge resection was performed in most women (90.48%). During the 3-year follow-up period, spontaneous intrauterine pregnancy was observed in 13 women (61.90%), 2 women (9.52%) became pregnant through artificial insemination treatment, and 6 women are not able to get pregnant (28.57%). None of the women experienced recurrent ectopic pregnancy.ConclusionThe postoperative pregnancy outcomes of women with ovarian pregnancy were encouraging. In this study, the spontaneous intrauterine pregnancy rate was favorable, and no cases of recurrent ectopic pregnancy were reported.     

高强度聚焦超声治疗有生育要求子宫腺肌病患者的妊娠结局

目的:探讨有生育要求的子宫腺肌病(AM)患者接受高强度聚焦超声(HIFU)治疗后的妊娠结局。方法:回顾分析2012年9月至2017年9月在中南大学湘雅三医院接受HIFU治疗的有生育要求的76例AM患者的临床资料。分析患者治疗后症状变化及妊娠结局,并与接受保守手术治疗的研究进行比较。结果:76例患者经HIFU治疗后,56例58次妊娠(妊娠组),中位妊娠时间为治疗后24个月,其中28例(30次)足月分娩,2例早产,20例自然流产,5例人工流产,1例异位妊娠。未妊娠组20例。患者治疗后月经及痛经症状较治疗前均有显著改善(P0.05)。19例不孕症患者经治疗后,15例成功受孕,妊娠率78.9%。有自然流产史的14例患者经治疗后,11例受孕,7例已足月分娩。与国外学者的保守手术临床研究比较,HIFU治疗后的妊娠率及足月分娩率均显著增高,差异有统计学意义(P均0.05),可选择自然分娩,无严重并发症发生。结论:HIFU用于治疗有生育要求的AM患者,可改善患者的妊娠结局,降低自然流产率,分娩方式可选择自然分娩,同时不增加妊娠及分娩时并发症发生率,是一种有效的治疗方式。     

Factors associated with withdrawal bleeding after administration of oral micronized progesterone in women with secondary amenorrhea.

OBJECTIVE: To compare two dosages of oral micronized progesterone (P) and placebo for withdrawal bleeding and side effects. DESIGN: Prospective, randomized, double-blind. SETTING: Academic institution. PARTICIPANTS: Out of 190 screened with oligomenorrhea/amenorrhea, 60 who qualified completed the study. INTERVENTIONS: A 10-day course of (1) oral micronized P 300 mg, (2) oral micronized P 200 mg, or (3) placebo. MAIN OUTCOME MEASURES: Withdrawal bleeding, side effects, and changes in lipids. Endogenous estradiol (E2) concentrations at baseline and P concentrations during treatment were correlated with bleeding response. RESULTS: Withdrawal bleeding occurred in 90% of women taking 300 mg, 58% of women taking 200 mg, and 29% of women taking placebo (P less than 0.0002 for 300 mg versus placebo). Side effects occurred similarly among the groups (P = not significant). Lipid concentrations were unchanged. Endogenous E2 and treatment P concentrations were of limited predictive value for withdrawal bleeding. CONCLUSIONS: Progesterone 300 mg induced significantly more withdrawal bleeding than placebo, with similar side effects. Bleeding response cannot be predicted reliably from E2 and P concentrations.     

Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review

Objective

The objective of this review was to analyze published contemporary oncologic and reproductive outcomes in women with endometrial hyperplasia or cancer undergoing medical management with progestin therapy.

Methods

A systematic review of oncologic and pregnancy outcomes in women with complex atypical hyperplasia or grade 1 adenocarcinoma was performed using a comprehensive search of the MEDLINE literature. English language studies published from 2004 to 2011 which utilized hormonal therapy were identified using key words endometrial hyperplasia, endometrial cancer, fertility preservation, hormone and progestin therapy. Fisher's exact test was used to calculate statistical differences.

Results

Forty-five studies with 391 study subjects were identified. The median age was 31.7 years. Therapies included medroxyprogesterone (49%), megestrol acetate (25%), levonorgestrel intrauterine device (19%), hydroxyprogesterone caproate (0.8%), and unspecified/miscellaneous progestins (13.5%). Overall, 344 women (77.7%) demonstrated a response to hormonal therapy. After a median follow up period of 39 months, a durable complete response was noted in 53.2%. The complete response rate was significantly higher for those with hyperplasia than for women with carcinoma (65.8% vs. 48.2%, p = .002). The median time to complete response was 6 months (range, 1-18 months). Recurrence after an initial response was noted in 23.2% with hyperplasia and 35.4% with carcinoma during the study periods (p = .03). Persistent disease was observed in 14.4% of women with hyperplasia and 25.4% of women with carcinoma (p = .02). During the respective study periods, 41.2% of those with hyperplasia and 34.8% with a history of carcinoma became pregnant (p = .39), with 117 live births reported.

Conclusion

Based on this systematic review of the contemporary literature, endometrial hyperplasia has a significantly higher likelihood of response (66%) to hormonal therapy than grade 1 endometrial carcinoma (48%). Disease persistence is more common in women with carcinoma (25%) compared to hyperplasia (14%). Reproductive outcomes do not seem to differ between the cohorts.     

Analysis of IVF/ICSI outcomes in infertile women with early-stage endometrial cancer and atypical endometrial hyperplasia after conservative treatment

Journal of Assisted Reproduction and Genetics - To investigate the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes and identify factors that might affect live births in...