Should women with chronic pelvic pain have adhesiolysis?

BACKGROUND: Pelvic adhesions are found in up to 50% of women with CPP during investigative surgeries and adhesiolysis is often performed as part of their management although the causal or casual association of adhesions, and the clinical benefit of adhesiolysis in the context of CPP is still unclear. Our aim was to test the hypothesis of whether laparoscopic adhesiolysis leads to significant pain relief and improvement in quality of life (QoL) in patients with chronic pelvic pain (CPP) and adhesions. METHODS: This was a double-blinded RCT. This study was conducted in 2 tertiary referral hospitals in United Kingdom over 4 years. Women with chronic pelvic pain (CPP) were randomized into having laparoscopic adhesiolysis or diagnostic laparoscopy. Women were assessed at 0, 3 and 6 months for Visual analogue scale scores (VAS) and Quality of Life (QoL) measures (SF-12 and EHP-30). RESULTS: A total of 92 participants were recruited; 50 qualified to be randomized, with 26 in the adhesiolysis and 24 in the control group. The results are expressed in median (interquartile ranges). In women who underwent adhesiolysis, there was a significant improvement at 6 months in VAS scores (-17.5 (-36.0 - -5.0) compared to controls (-1.5 (-15.0 - 4.5; p = 0.048); SF-12 scores physical component score (25.0 (18.8 - 43.8)) compared to controls (6.3 (-6.3 - 18.8); p = 0.021), SF-12 emotional component score 32.5 (4.4 - 48.8) compared to controls -5 (-21.3 - 15.0); p < 0.0074) and EHP-30 emotional well being domain 32.5 (4.4 - 48.8) compared to the controls -5 (-21.3 - 15.0; p < 0.0074). CONCLUSIONS: This study stopped before recruitment reached the statistically powered sample size due to difficulty with enrollment and lack of continued funding. In selected population of women presenting to the gynecological clinic with chronic pelvic pain, adhesiolysis in those who have adhesions may be of benefit in terms of improvement of pain and their quality of life. TRIAL REGISTRATION NUMBER: ISRCTN 43852269.

Green tea extract as a cryoprotectant additive to preserve the motility and DNA integrity of human spermatozoa.

Cryopreservation impairs sperm quality and functions, including motility and DNA integrity. Antioxidant additives in sperm freezing media have previously brought improvements in postthawed sperm quality. Green tea extract (GTE) is widely considered as an excellent antioxidant, and its beneficial role has been proven in other human cells. This study aims to evaluate the GTE as a potential additive in cryopreservation media of human spermatozoa. In part one, the semen of 20 normozoospermic men was used to optimize the concentration of GTE that maintains sperm motility and DNA integrity against oxidative stress, induced by hydrogen peroxide (H2O2). Spermatozoa were treated with GTE at different concentrations before incubation with H2O2. In part two, the semen of 45 patients was cryopreserved with or without 1.0 ng ml-1 GTE. After 2 weeks, the semen was thawed, and the effect on sperm motility and DNA fragmentation was observed. Our data showed that GTE significantly protected sperm motility and DNA integrity against oxidative stress induced by H2O2when added at a final concentration of 1.0 ng ml-1. We found that the addition of 1.0 ng ml-1 GTE to cryopreservation media significantly increased sperm motility and DNA integrity (both P < 0.05). More interestingly, patients with high sperm DNA damage benefited similarly from the GTE supplementation. However, there was no significant change in the reactive oxygen species (ROS) level. In conclusion, supplementing sperm freezing media with GTE has a significant protective effect on human sperm motility and DNA integrity, which may be of clinical interest.

Circulating levels of matrix proteases and their inhibitors in pregnant women with and without a history of recurrent pregnancy loss.

BACKGROUND: We have recently shown that serum relaxin-2 levels are attenuated in women with a history of recurrent pregnancy loss (RPL). We sought to determine whether a history of RPL is also associated with changes in serum matrix metalloproteases (MMPs) and tissue inhibitors of matrix metalloproteases (TIMP) -1 and -2. METHODS: We obtained serum from 20 pregnant women with a history of RPL and 20 age-matched pregnant women with no history of RPL (NRPL) at 6-8, 10-12, 20, and 34 weeks gestation, and from cord blood. We quantified total serum concentrations of MMP-1, MMP-3, MMP-9 and TIMP-1 and TIMP-2 by ELISA. We determined whether these serum marker levels were associated with a history of RPL and delivery before 37 weeks gestation. RESULTS: There was no difference in the rates of miscarriage, preterm birth or prelabour rupture of fetal membranes between RPL and NRPL. However babies born to RPL were lighter than those born to NRPL. Serum MMP-1, 9, and TIMP-1 did not differ between RPL and NRPL but MMP-3 was higher in RPL vs. NRPL at 6-8 weeks (P < 0.05). Serum TIMP-2 levels were higher in RPL women at all gestations (P < 0.01). The ratio of RLX-2 (reported previously) to TIMP-2 at 10-12 weeks gestation was more strongly associated with a history of RPL than either peptide separately - area under the ROC curves for RLX-2 0.79 (95% CI 0.57 to 0.92), TIMP-2 0.83 (95% CI 0.63 to 0.95), and for RLX-2:TIMP-2 ratio 0.92 (95% CI 0.74 to 0.99). CONCLUSIONS: Women with a history of RPL demonstrate increased serum TIMP-2 and reduced RLX-2 during a subsequent viable pregnancy. Determination of both markers in early pregnancy enhances the discrimination of women with a history of RPL. These observations suggest roles for these two peptides in early implantation and placental development. Whether these may prove to be reliable early predictive markers for subsequent pregnancy loss in the index pregnancy is unknown and will require further studies.

Ultrastructural features of endometrial-myometrial interface and its alteration in adenomyosis.

The endometrial-myometrial interface (EMI) is a specific functional region of uterus. However, our knowledge on EMI ultrastructure both in normal uterus and adenomyosis is far from enough to understand its pathology. In this study, used the samples of EMI and outer myometrium (OM) from the adenomyosis hysterectomy specimens and the subjects from the control uteri, we prospectively compared the ultrastructure of myocytes from EMI and OM, the ultrastructural changes of EMI between the proliferative and secretory phases, and the ultrastructural difference of EMI between adenomyosis and the control group. In both adenomyosis and control group, there were differences in ultrastructure between myocytes from EMI and OM. Specifically, the myocytes from EMI were rich in organelles. In contrast, the myocytes from OM had abundant contractile structural components. In the proliferative phase, the myocytes from EMI in adenomyosis had significantly smaller cell and nucleus diameter than those from the control group, but in the secretory phase, the difference was not significant. In the control group, the various ultrastructural features of myocytes from EMI including the mean diameter of cell and nuclei and the myofilaments/cytoplasm ratio exhibited cyclical changes, but in adenomyosis, the normal cyclical changes were absent. In conclusions, there are significant ultrastructural differences between the myocytes from EMI and OM. The myocytes in women with adenomyosis were significantly different to the control subjects, primarily because the normal cyclical changes were absent.

Uterine natural killer cells in peri-implantation endometrium from women with repeated implantation failure after IVF.

Several studies have suggested that endometrial uNK (CD56+) cells may play a role in implantation. The aim of this study was to investigate the number of CD56+, CD16+ and CD69+ cells in the unstimulated endometrium of women with recurrent implantation failure after IVF. The percentage of stromal cells positive for CD56, CD16 and CD69 was identified by immunocytochemistry in endometrial biopsies from 15 normal control women and 40 women with recurrent implantation failure. All biopsies were obtained on days LH+7 to LH+9. The density of CD56+ cells in endometrium from women with repeated implantation failure after IVF [median (range) CD56+ cell density=14.5% (1.5-71.4%)] was significantly higher (P=0.005) than in endometrium from control women [5% (2.1-19.2%)]. There was no significant difference in the densities of CD16+ and CD69+ cells in the endometrium from women in the two groups. The increased density of CD56+ cells in the endometrium of women with recurrent implantation failure suggests that these cells are directly involved in the implantation process; alternatively this may indicate a general endometrial defect in these women, which leads to the inability of the embryo to implant.

Serum relaxin levels are reduced in pregnant women with a history of recurrent miscarriage, and correlate with maternal uterine artery Doppler indices in first trimester.

OBJECTIVES: Defective implantation is a mechanism for recurrent pregnancy loss (RPL). We sought to determine whether the serum expression of human relaxin-2 (RLX) is impaired in women with a history of RPL. STUDY DESIGN: Employing a prospective case-controlled design we studied 20 pregnant women with a history of RPL and 20 age-matched women with no history of RPL (NRPL). We measured serum relaxin-2 levels by ELISA at 6-8, 10-12, 20, and 34 weeks gestation and in cord blood, and maternal uterine artery Doppler resistance index (RI) at >or=10 weeks gestation. RESULTS: Relaxin rose to a peak at 12 weeks, and gradually declined towards term. At all gestations, women with a history of RPL had lower RLX levels than women without. At 10-12 weeks gestation, uterine artery RI correlated with serum RLX for both RPL and NRPL. In the NRPL group at 10-12 weeks the presence of a notched waveform was associated with higher RLX levels than the absence of a notch (mean 2.1 ng/ml vs. 1.3 ng/ml, P<0.05) and also at 20 weeks (2.1 ng/ml vs. 0.95 ng/ml, P<0.05) but no such difference was seen in the RPL group. Umbilical venous RLX was 4-fold higher in the RPL group than the NRPL group. CONCLUSION: Women with a history of RPL demonstrate attenuated levels of serum RLX across all pregnancy trimesters. How dysregulated RLX metabolism may contribute to adverse pregnancy outcome in RPL requires further investigation.

Preliminary prospective study of the endocrinology of conception cycles and early pregnancy in women with antiphospholipid syndrome treated with low molecular weight heparin.

OBJECTIVE: To examine whether there were any differences in the endocrinological profiles during conception cycle and early pregnancy between a control group and women with a history of recurrent miscarriage that was caused by antiphospholipid syndrome and that was treated with aspirin and low molecular weight heparin. DESIGN: Prospective observational study. SETTING: Recurrent Miscarriage Clinic, Department of Obstetrics and Gynaecology in a tertiary care centre. PATIENT(S): Five women with recurrent pregnancy loss were recruited as cases, whereas another five women having natural cycle donor insemination were used as control. INTERVENTION(S): Serial measurement of serum beta-hCG, activin A, and inhibin A was performed from postovulatory day 12 until 11 weeks of gestation. MAIN OUTCOME MEASURE(S): Comparison of levels of beta-hCG, activin A, and inhibin A at the time of conception onwards till 11 weeks in the two groups. RESULT(S): There were no significant differences between the two groups. CONCLUSION(S): There does not appear to be any obvious endocrinological alteration in the conception cycle of women with antiphospholipid syndrome compared with a control group. Furthermore, the initiation of heparin does not produce a significant change in activin A and inhibin A levels.

A study of luteal phase expression of inhibin, activin, and follistatin subunits in the endometrium of women with recurrent miscarriage.

OBJECTIVE: To compare the luteal phase endometrial expression of inhibin, activin, and follistatin subunits in women with recurrent miscarriage compared to a control group. Other parameters of luteal function assessed included Doppler blood flow, serum biochemical markers, and histopathology. DESIGN: This was a prospective case control study. SETTING: The study was conducted in a tertiary care hospital of Sheffield, United Kingdom. PATIENT(S): Thirty-three women with recurrent miscarriage and 10 women with no previous history of miscarriage (control group) were recruited. INTERVENTION(S): Histologic assessment of the luteal phase endometrium was done using Noyes criteria followed by immunohistochemical analysis for expression of inhibin, activin, and follistatin subunits. Doppler analysis for perifollicular and endometrial blood flow was also done. Simultaneously serum concentrations of E(2), LH, FSH, P, and inhibin B at the time of LH surge and at LH +7 days were measured. MAIN OUTCOME MEASURES: Difference in endometrial expression of inhibin, activin, and follistatin subunit in the two groups. RESULT(S): Endometrial expression of follistatin and beta A in the endometrial stromal cells of women with recurrent miscarriage was significantly lower than in control women. There were no differences in results of the Doppler studies or the hormonal profiles between cases and controls. CONCLUSION(S): The lower expression of follistatin and beta A subunit in women with recurrent miscarriage may imply an altered activity of activin A at the time of decidualization, which may lead to poor pregnancy outcome in the form of miscarriage.

Absence of follicular phase defect in women with recurrent miscarriage.

OBJECTIVE: The study was designed to compare the follicular phase of women with recurrent pregnancy loss and a healthy control group. It is possible that a defective or aberrant follicular phase may be associated with poor oocyte quality leading to a production of an embryo with compromised quality and hence early pregnancy loss. DESIGN: Prospective case-control study. SETTING: A tertiary care hospital of Sheffield, UK. PATIENT(S): Thirty-four women with recurrent miscarriage and 10 women with no previous history of miscarriage and regular menstrual cycles (control group) were recruited. INTERVENTION(S): The characteristics studied included Doppler assessment of blood flow to the follicle and the endometrium. Simultaneously, serum concentrations of biochemical markers such as anti-Müllerian hormone, inhibin B, FSH, LH, and P were compared in the two groups. MAIN OUTCOME MEASURE(S): Differences in the two groups. RESULT(S): We were unable to detect significant differences in various biochemical and ultrasound measurements in the follicular phase between women with recurrent miscarriage and a control group; however, the expected correlation between ovarian and pituitary hormones, which was observed in the control group, was absent in women with recurrent miscarriage. CONCLUSION(S): There may be subtle derangements of the feedback mechanism responsible for regulation of follicle development in this group of women. However, there were no obvious differences in the follicular phase of women with recurrent miscarriage and a healthy control group.

Inhibin A and activin A may be used to predict pregnancy outcome in women with recurrent miscarriage.

OBJECTIVE: To look at the role of inhibin and activin in predicting pregnancy outcome in patients with history of recurrent miscarriage. DESIGN: Observational clinical study. SETTING: Recurrent miscarriage clinic of a tertiary care teaching hospital. PATIENT(S): Patients with history of recurrent miscarriage. INTERVENTION(S): Serial serum inhibin A and activin A concentrations were measured in weeks 5 though 8 of pregnancy. MAIN OUTCOME MEASURE(S): Serum concentrations of inhibin A and activin A levels. RESULT(S): Mean inhibin A concentration at 5 to 6 weeks for women who miscarried and those who had live births was 33 and 51 pg/mL, respectively; activin A at same gestation for the two groups was 534 and 643 pg/mL, respectively. After 2 weeks, mean inhibin A concentration for women who miscarried and those who had live births was 66 and 145 pg/mL, respectively, and activin A was 747 and 1,123 pg/mL, respectively. CONCLUSION(S): It is possible that inhibin A and activin A may be used as markers to predict pregnancies that are likely to miscarry.

Surgical intervention in infertility management.

Despite improvement in the success of IVF, reproductive surgery will remain an important option and complement to assisted reproductive technologies (ART) for many couples. Reproductive surgery should be considered as the first-line treatment when the correction of infertility pathologies is simple and a good result is expected once corrected, when the pathology is causing symptoms such as pain or abnormal bleeding, or if uncorrected will compromise the results or increase the risks of ART. The success of surgical infertility treatment depends on the careful selection of cases using appropriate investigative techniques, with procedures performed in centres with sufficient expertise. For both specialized reproductive and general gynaecological surgery it is crucial to follow microsurgical principles to avoid adhesion formation and conserve normal tissues, especially tubal and ovarian. These aspects of reproductive surgery, and different surgical techniques used for various tubal, peritoneal, uterine and ovarian conditions to achieve the optimal reproductive outcome are discussed in this article.