Long-term reproductive performance after surgery for ovarian endometrioma

Mainresultsandtheroleofchance: Therelativemedianfolddifferenceof IGF2 gene expression in eCG and hMG cohorts resulted in a 2-3 times decrease in the expression levels of 0.23 + 0.39 and 0.18 + 0.13 versus 0.56 + 0.7 in control (P , 0.05), while 5IU Pergoveris was comparable. H19 and IGF2r mRNA tran-scripts were equivalent between the groups compared to unstimulated control. Both the eCG and hMG cohorts displayed increased live birth rates of 67 and 75% (P , 0.05 and P , 0.001 respectively) compared to 50% in un-stimulated and Pergoveris groups. Analysis of progeny suggested ovarian stimulation also reduced the relative heart and lung weights of day 10 neonates compared to unstimulated controls (P , 0.05). Limitations, reason for caution: Gene homology between mice and human is estimated at 99% but mice are polyovulatory and have short cycles so the effects of ovarian stimulation in the mouse may differ from the human. Further, the gonadotrophins used for superovulation were heterologous although differences were observed between human recombinant and urinary preparations. Wider implications of the ﬁndings: This study conﬁrms and extends data in the literature to show that superovulation with speciﬁc gonadotrophin preparations mayperturbexpressionofimprintedgenesandresult inabnormalorgandevelop- ment in the offspring. The incidence of the IGF2 related Beckwith Weidemann syndrome is known to be more prevalent in children born through assisted repro- ductive technologies. The results of the present study suggest that these effects may be related to the use of speciﬁc ovarian stimulation drugs. Studyfunding/competinginterest(s): StudyfundingcamefromtheNottingham university research and treatment unit for reproduction and embryology (NURTURE) and the University of Nottingham. The laser for trophectoderm biopsy was provided by Hamilton Thorne. Wider implications of the ﬁndings: Our study complements an ultrasound follow-up study, 1 that showed follicular formation in previously detorted ovaries. We found that fever, leukocytosis and raised CRP have overall poorer histological outcomes. Post-menopausal torsions radiologically resemble malig-nancy pre-operatively, and are less tolerant to ischaemia. Young patients with shorter duration ( , 12 hours) have better prognosis. Variation in preservation in prolonged periods of torsion ( . 70 hours) could be due to other factors, such as tightness at the neck of the torsion. Study funding/competing interest(s): None Study question: What is, in women with tubal ectopic pregnancy (EP) and a normal contra lateral tube, the impact of salpingotomy and salpingectomy on ﬁ- nancial costs. Summaryanswer: Salpingotomyismoreexpensivethansalpingectomyperran- domised woman.

Main results and the role of chance: The relative median fold difference of IGF2 gene expression in eCG and hMG cohorts resulted in a 2-3 times decrease in the expression levels of 0.23 + 0.39 and 0.18 + 0.13 versus 0.56 + 0.7 in control (P , 0.05), while 5IU Pergoveris was comparable. H19 and IGF2r mRNA transcripts were equivalent between the groups compared to unstimulated control. Both the eCG and hMG cohorts displayed increased live birth rates of 67 and 75% (P , 0.05 and P , 0.001 respectively) compared to 50% in un-stimulated and Pergoveris groups. Analysis of progeny suggested ovarian stimulation also reduced the relative heart and lung weights of day 10 neonates compared to unstimulated controls (P , 0.05). Limitations, reason for caution: Gene homology between mice and human is estimated at 99% but mice are polyovulatory and have short cycles so the effects of ovarian stimulation in the mouse may differ from the human. Further, the gonadotrophins used for superovulation were heterologous although differences were observed between human recombinant and urinary preparations. Wider implications of the findings: This study confirms and extends data in the literature to show that superovulation with specific gonadotrophin preparations may perturb expression of imprinted genes and result in abnormal organ development in the offspring. The incidence of the IGF2 related Beckwith Weidemann syndrome is known to be more prevalent in children born through assisted reproductive technologies. The results of the present study suggest that these effects may be related to the use of specific ovarian stimulation drugs. Study question: What is the long-term impact of surgery for ovarian endometriomas on reproductive performance and age of menopause? Summary answer: Surgery for ovarian endometrioma per se does not appear to affect women's long-term reproductive performance or age of menopause. What is known already: Surgery for endometrioma has been shown to damage ovarian reserve. The effect of this damage on reproductive performance remains uncertain. A recent study on ablative surgery for ovarian endometriomas reported a long-term pregnancy rate of 76% (including spontaneous and in-vitro fertilisation pregnancies). However, the long-term impact of other types of surgery for ovarian endometriomas on reproductive performance remains to be investigated. Study design, size, duration: This was a longitudinal observational cohort study including 68 patients who had undergone different types of surgery for ovarian endometriomas between January 1999 and December 2009. The study also included 68 age-and weight-matched healthy controls. Participants/materials, setting, methods: Hospital records were reviewed and each participant was asked to complete a questionnaire and attend an interview. Long-term pregnancy rates were compared between the two groups. Pregnancy rates were also compared in endometrioma patients before and after surgery.
Age of menopause was compared in post-menopausal women in the two groups.
Main results and the role of chance: Amongst the 38 women desiring fertility after endometrioma surgery, 19 (50%) achieved spontaneous pregnancy during the follow-up period. This was not significantly different from a pre-operative pregnancy rate of 48% (22/46). Of these 19 patients, four achieved another pregnancy with fertility treatment. An additional eight patients conceived only with the help of fertility treatment, giving an overall long-term post-operative pregnancy rate of 71% (27/38). These results were significantly lower (p ¼ 0.0001) than the 98% (57/58) long-term natural pregnancy rate in the control group. Pregnancy rates in patients receiving fertility treatment significantly (p ¼ 0.001) increased from 7% (1/15) before surgery to 63% (12/19) post-operatively. In post-menopausal women, the median (quartile) age at menopause was similar in the study (n ¼ 9) and control groups (n ¼ 6) [48(45-52) vs. 49(44-52)years, respectively] Limitations, reason for caution: The main limitation of this study is its retrospective design which could have introduced potential bias. Wider implications of the findings: Endometriomas per se appear to be the main cause of the reduced long-term reproductive function of the affected patients, with little or no contribution from surgery. Furthermore, endometrioma surgery seems to improve the success rates of fertility treatment. These findings are reassuring for patients with endometrioma who are seeking fertility and need surgery for their disease. Study question: Are there any clinical predictors of ovarian histological preservation? Study the impact of ovarian torsion on ovarian tissue, particularly the ovarian follicles. Summary answer: The Oocyte Preservation Score(OPS) was developed in order to evaluate histopathological changes of ischaemia and infarction. Fever, leucocytosis, raised CRP and menopause where associated with lower oocyte preservation. In some cases, good ovarian preservation was observed even at prolonged periods of torsion. Preserved oocyte follicles were observed in 42/67(62.6%). What is known already: Good clinical outcomes are reported on detorsion of all torted ovaries, irrespective of appearance, in a clinical and ultrasound follow-up study (N ¼ 102). 1 They reported .91% subsequent follicular development in the previously torted ovary, of whom 6/6 had successful IVF. 1 In rodents, the histological changes of ischaemia can resolve within 24 hours, when the torsion has occurred for less than 36 hours. Such a watershed time interval has not been shown in humans. 2 Study design, size, duration: Re-examination of pathology specimens and retrospective review of clinical notes at a major London teaching hospital. Study period from 1999 to 2010. A total of 72 patients with confirmed ovarian torsion at surgery were identified. 58/72 (80.5%) had a complete clinical and pathology data available. Participants/materials, setting, methods: Two novel scoring systems (oocyte preservation score (OPS) and tissue necrosis score (TNS)) were developed to evaluate the effect of torsion on ovarian tissue. OPS grades: low (4, 6,) and high (8, 10) preservation. Clinical predictors of ovarian histological preservation were assessed using parametric statistics and multiple linear regression modelling. Main results and the role of chance: 58/72 had a complete set of clinical and pathology data. Mean age was 38 + 4.2(17-86) years. 44/58(75.8%) pre-menopausal. 25/44(56.8%) were premenopausal nulliparous, with mean age 26.7(range 17-39) years. 5/44 (11.3%) during pregnancy (7, 13, 16, 20, and 34 weeks). 23/ 67(34.3%) had no other pathology. 1/67 malignancy (adult granulosa cell tumour).
Oocytes and ovarian follicles located in the ovarian cortex were the last part of the ovary to be affected (OPS 4 and 6). Limitations, reason for caution: We are limited by the quality of documentation in clinical notes. Length of ischaemia was assumed to reflect length of time in pain during that clinical episode. There may be overestimate, underestimate and clinical documentation inaccuracy of pain duration. This may only be eliminated in a prospective study.

Abstracts i75
Downloaded from https://academic.oup.com/humrep/article-abstract/28/suppl_1/i75/660791 by guest on 28 July 2018 Wider implications of the findings: Our study complements an ultrasound follow-up study, 1 that showed follicular formation in previously detorted ovaries. We found that fever, leukocytosis and raised CRP have overall poorer histological outcomes. Post-menopausal torsions radiologically resemble malignancy pre-operatively, and are less tolerant to ischaemia. Young patients with shorter duration (,12 hours) have better prognosis. Variation in preservation in prolonged periods of torsion (.70 hours) could be due to other factors, such as tightness at the neck of the torsion. Study question: What is, in women with tubal ectopic pregnancy (EP) and a normal contra lateral tube, the impact of salpingotomy and salpingectomy on financial costs. Summary answer: Salpingotomy is more expensive than salpingectomy per randomised woman. What is known already: We have recently reported that in women with tubal EP in the presence of a normal contralateral tube salpingotomy and salpingectomy result in equal pregnancy rates. Salpingotomy requires more operating time and bears the risk of persistent trophoblast (PT) necessitating additional treatment. Both after salpingotomy and salpingectomy there is a risk of repeat ectopic pregnancy. This implies potentially higher costs after salpingotomy. An economic evaluation of salpingotomy compared to salpingectomy including repeat ectopic pregnancy is not available. Study design, size, duration: We performed a randomised controlled multicentre study between September 2004 and November 2011. Women were allocated to salpingotomy (n ¼ 221) or salpingectomy (n ¼ 233) in case of a tubal ectopic pregnancy and a normal contra lateral tube. Fertility follow-up was done up to 36 months. Participants/materials, setting, methods: We now compared direct medical costs of salpingotomy and salpingectomy until a spontaneous ongoing pregnancy within a time-horizon of 36 months. Direct medical costs included treatment for the index EP, re-interventions, PTand repeat EP. The analysis was done according to the intention to treat principle. Main results and the role of chance: Ongoing pregnancy rates were 114 of 213 women (53.5%) in the salpingotomy group and 121 of 234 (51.7%) in the salpingectomy group. Data for the economic analysis were available in 447 of the 454 (98.5%) randomised women. After salpingotomy, direct medical costs were higher because of more surgical re-interventions, treatment for PT and repeat EPs. Per randomised woman, these costs were E3.408 for salpingotomy and E2.714 for salpingectomy (mean difference E 694). Limitations, reason for caution: These results are based on the cost structure of one hospital, whereas costs differ largely between countries. Sensitivity analyses will be required to evaluate the impact of differences in resource use and costs. Wider implications of the findings: Per woman with an ectopic pregnancy, the costs of salpingotomy are higher than for salpingectomy, for no additional medical benefit. These results suggest that in women with tubal EP and a normal contra lateral tube, salpingectomy is the preferred treatment. Study question: We aim to test the hypothesis that laparoscopic adhesiolysis leads to significant pain relief and improvement in quality of life (QoL) in patients with chronic pelvic pain (CPP) and adhesions. Summary answer: Removal of adhesions laparoscopically in women with chronic pelvic pain improves quality of life at 6 months What is known already: Many observational studies have shown that in patients with adhesions and CPP, the surgical removal of adhesions significantly alleviates CPP although this is not a universally shared view. Nevertheless, adhesiolysis is increasingly being performed for the treatment of CPP, although the effectiveness of adhesiolysis as a treatment of CPP is yet to be tested robustly by randomised controlled trials for treatment, the gold standard for evidence-based medicine. Study design, size, duration: This is a double blind RCT randomising patients to laparoscopic adhesiolysis or diagnostic laparoscopy. It was conducted over 4 years in 2 hospitals in the UK. Women were assessed at 0,3 and 6 months for Visual analogue scale scores (VAS)and QoL measures (SF-12 and EHP-30)). Participants/materials, setting, methods: A total of 92 participants were recruited; 42 qualified to be randomized at laparoscopy to either adhesiolysis or not. Randomisation was computer generated with allocation concealment. The study was powered for a recruitment sample size of n ¼ 200, with n ¼ 100 randomised patients; an interim analysis planned. Main results and the role of chance: There was no difference in the baseline characteristics between the study and control groups (age, baseline adhesion and QoL scores). Women who had adhesiolysis scored significantly better at 6 months in SF-12 (both physical and emotional components) and EHP-30 (in pain and emotional well-being domains) (p , 0.01). There was no significant difference in visual analogue score (VAS) at 6 months (p ¼ 0.07). VAS scores at baseline were higher (worst) in those patients with bowel adhesions (median VAS score 49, IQR 22-66) compared to those without (median VAS score 18, IQR 7-51, p , 0.05). This study prematurely terminated due to significant differences in the main QoL outcome measures and the lack of continued funding over the prolonged duration of the study. Limitations, reason for caution: Due to the premature termination of the study, we are unable to assess the impact of adhesiolysis on pain with sufficient power. Despite this, the significant findings in QoL improvement would suggest that it would be unethical to continue the study in its present form. Wider implications of the findings: In the select population of women presenting to the gynecological clinic with chronic pelvic pain, adhesiolysis in those who had adhesions is of benefit in terms of improvement of their quality of life. However, these findings may be confined to tertiary hospitals in the UK with a specialised endoscopy service.