T.C. Li

Effect of increased body mass index on oocyte and embryo quality in IVF patients

Obesity may have an adverse effect on the outcome of IVF/intracytoplasmic sperm injection (ICSI) treatment. In this study, the effects of increased body mass index (BMI) on oocyte and embryo quality during IVF cycles were studied. A retrospective analysis of 426 IVF/ICSI cycles was performed. Cycles were classified according to the BMI: normal BMI (19-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)) and obese (> or = 30 kg/m(2)). Cycles were further stratified based on age (group 1, < 35 years; group 2, > or = 35 years). Markers of oocyte quality (number of oocytes inseminated and fertilization rate) and embryo quality (utilization rate, number of embryos discarded and cryopreserved, and mean embryo grade) were examined. In group 1, obesity had a significant adverse effect on the mean embryo grade (P = 0.02), the embryo utilization rate (P = 0.01), number of embryos discarded (P = 0.007) and cryopreserved (P < 0.05). In group 2, there was no difference in markers of embryo quality between the three BMI ranks. Obesity did not have any significant effect on markers of oocyte quality or clinical pregnancy rates. In conclusion, obesity may adversely affect embryo quality in young women (<35 years) undergoing IVF/ICSI, while the oocyte quality is not affected.

Cytokine expression in the endometrium of women with implantation failure and recurrent miscarriage

One potential cause of reproductive failure such as infertility and recurrent miscarriage may be an endometrial defect. Numerous studies in mice have suggested the importance of various different cytokines in successful pregnancy outcome. This article reviews the literature available on the role of T helper cytokines and IL-1, IL-11, LIF, IL-12 and IL-18 in infertility and recurrent miscarriage, with particular emphasis on the role that endometrial cytokines may play. Although there are numerous studies on cytokines in recurrent miscarriage, much less has been reported on their role in infertility with or without failure after IVF. There is also considerable variation in the results obtained from various different studies, which may be due to different populations studied, the different timing of the sample collection, and whether the cytokines were measured in whole tissue or a specific cell population. The presence of complicated networks of cytokines and their overlapping biological activities means that alteration of one cytokine is likely to affect others and this also makes the study of their role in implantation failure very difficult. There is an urgent need to re-examine the role played by various cytokines in reproductive failure through carefully planned and vigorously designed studies and to compare the different types of reproductive failure.

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.

Laparoscopic surgery for endometriosis : How often do we need to re-operate?

Summary This study aimed to examine the rate of re-operation in women with endometriosis over a 10-year period. This was a retrospective study set in a university hospital in the UK. Notes of all women diagnosed with endometriosis were reviewed and data entered on a standard proforma. A total of 486 out of 988 procedures were for treatment of endometriosis. Some 240 (49%) had pelvic pain and 246 (51%) had subfertility. The mean age of those women who had a re-operation was lower than those who did not have any further operations. Using logistic regression, three factors were found to be the most important factors influencing the likelihood of women having re-operation – in decreasing order of importance, these factors were: (1) age, (2) pregnancy achievement and (3) improvement of symptoms. Re-operation occurred in 51% of our study population, the information may be useful for guidance of our patients.

The value of measuring anti-Müllerian hormone in women with anovulatory polycystic ovary syndrome undergoing laparoscopic ovarian diathermy

BACKGROUND Anti-Müllerian hormone (AMH) has been implicated in the pathogenesis of polycystic ovary syndrome (PCOS). The aim of this study was to measure circulating AMH before laparoscopic ovarian diathermy (LOD) to evaluate its prognostic value for an ovulatory response and to investigate AMH changes after LOD to further explore the effects of LOD. METHODS This prospective study included anovulatory women with PCOS undergoing LOD (n = 29) or receiving clomiphene citrate (n = 18). Plasma AMH concentrations were measured before and 1 week after treatment. Further measurements of AMH were made at 3- and 6-month follow-up. RESULTS The pretreatment median (range) plasma AMH concentrations were 6.1 (1.0-21.0) and 5.7 (1.3-9.5) ng/ml in women having LOD and clomiphene citrate treatment, respectively. Women who ovulated after LOD (n = 24) had a significantly (P = 0.032) lower pre-operative AMH [5.6 (1.0-21.0) ng/ml] compared with the non-responders [9.0 (6.1-17.1) ng/ml]. Using receiver-operating characteristic curve analysis, AMH was found to be a useful predictor of no ovulation after LOD with area under the curve of 0.804 (P = 0.025). Using a cut-off of 7.7 ng/ml, AMH had a sensitivity of 78% and a specificity of 76% in the prediction of no ovulation after LOD. For all patients (n = 47, clomiphene citrate or LOD), plasma AMH >or=7.7 ng/ml was associated with a reduced chance of ovulation after treatment (P = 0.004). Following LOD, the median AMH concentration significantly (P = 0.003) decreased to 4.7 (0.3-15.1) ng/ml and remained low at 3- and 6-month follow-up. CONCLUSIONS Pretreatment circulating AMH level seems to be a good predictor of the ovarian response to LOD.

Randomized controlled trial comparing laparoscopic ovarian diathermy with clomiphene citrate as a first-line method of ovulation induction in women with polycystic ovary syndrome

BACKGROUND Laparoscopic ovarian diathermy (LOD) is currently accepted as a successful second-line treatment for ovulation induction (OI) in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome (PCOS). The aim of this study was to test the hypothesis that LOD may be superior to CC as a first-line treatment. METHODS The study included 72 anovulatory women with PCOS who were randomized to LOD (n = 36) or CC (n = 36). Women who remained anovulatory after LOD were offered CC. Similarly, women receiving CC who failed to ovulate or conceive were offered LOD. Pregnancy rates were compared between the two groups using chi(2) and odds ratio with 95% confidence interval (OR, 95% CI). RESULTS After randomization, six women conceived before starting treatment and another patient postponed treatment. The remaining 65 women received the treatment (33 underwent LOD and 32 received CC). After the primary treatment, more pregnancies (44%) occurred in women receiving CC than in those undergoing LOD (27%), although the difference did not reach statistical significance [P = 0.13, OR 2.1 (0.7 - 5.8)]. After adding the second treatment, the pregnancy rate was still higher, but to a less extent, in the CC group [63% versus 52%, P = 0.2, OR 1.6 (0.6 - 4.2)]. CONCLUSIONS LOD is not superior to CC as a first-line method of OI in women with PCOS. The trial is registered with ClinicalTrials.gov with an identifier number NCT00220545.

To close or not to close? A systematic review and a meta-analysis of peritoneal non-closure and adhesion formation after caesarean section

Many gynaecologists do not currently close the peritoneum after caesarean section (CS). Recently, several studies examining adhesion formation after repeat CS appear to favour closure of the peritoneum after caesarean section. We performed a systematic review of the current available evidence with regard to the long-term outcome, mainly in terms of adhesion formation after closure versus non-closure of peritoneum during CS. We undertook a literature search between January 1995 and February 2008 using MEDLINE, Pubmed, EMBASE, Cochrane central controlled trials register and Cochrane pregnancy and childbirth group trials register. We also had searched all the references cited in the relevant studies. Both English and non-English language papers were included. Prospective studies which compared peritoneal closure versus non-closure during CS in terms of adhesion formation were included. Studies were included if they had a primary objective to examine adhesion formation in a repeat caesarean section, had a clear study design, had an adhesion scoring system, excluded patients who had adhesions in the primary caesarean section or interim surgeries after the primary caesarean section, and had no usage of anti-adhesion agents in the primary caesarean section. Retrospective studies which were performed by case-notes review alone, were excluded. Eleven studies were identified via our search strategy. Five were retrospective and six were prospective. Out of the eleven studies, three satisfied the inclusion criteria and were included (n=249); two studies were follow-ups of RCTs and one was not randomised. Out of 249 women included in the analysis, 110 had peritoneal closure during CS whereas the other 139 did not have peritoneal closure. Meta-analysis was performed using the two randomised studies plus (i) the unadjusted estimate from the non-randomised study and (ii) the reported adjusted estimate, adjusted for baseline differences in the groups. Non-closure of the peritoneum during CS resulted in a significantly increased likelihood of adhesion formation in both meta-analyses--OR (95% CI): (i) 2.60 (1.48-4.56) and (ii) 4.23 (2.06-8.69). This systematic review has demonstrated that according to current data in the literature, there is some evidence to suggest that non-closure of the peritoneum after caesarean section is associated with more adhesion formation compared to closure.

Expression of leukaemia inhibitory factor and interleukin 15 in endometrium of women with recurrent implantation failure after IVF; correlation with the number of endometrial natural killer cells

BACKGROUND Several studies have suggested that endometrial interleukin 15 (IL-15) and the leukaemia inhibitory factor (LIF) may be important in embryo implantation. IL-15 is postulated to play a role in the control of uterine natural killer (uNK) cell proliferation and function, and uNK cells are also known to play a role in implantation. The aims of this study was to (1) compare endometrial levels of IL-15 and the LIF in women with recurrent implantation failure (RIF) after IVF with those in fertile women (controls) and (2) examine the relation of IL-15 and LIF levels to the uNK cell number. METHODS We investigated IL-15 and LIF in precisely timed endometrial biopsies (days LH + 7-LH + 9, where the day of the LH surge is LH + 0) obtained from control women (n = 15) and women with RIF (n = 45) by immunohistochemistry. A semi-quantitative analysis was performed by the H-score analysis of staining intensity in the stroma, glandular epithelium and luminal epithelium, separately. We also correlated expression of LIF and IL15 with uNK cell numbers (obtained in an earlier study of the same samples). RESULTS The quantity of the LIF protein in endometrial glandular epithelium in women with RIF [median and range; 179 (70-365)] was lower (P = 0.01) than in control women [median and range; 247 (120-287)]. In contrast, the level of the IL-15 protein in the stroma in women with RIF [median and range; 90 (0-175)] was higher (P = 0.009) than in control women [median and range; 60 (15-150)]. There was a significant correlation between the uNK cell number and stromal expression of IL-15 (r = 0.427, P = 0.001). No correlation between the LIF expression in any compartment and the uNK cell number was seen. CONCLUSIONS The results show an altered expression of LIF and IL-15 in the endometrium of women with RIF. Despite the limitation of not identifying uNK cells by phenotypic markers, the correlation between the uNK cell number and the stromal cell IL-15 suggests that IL-15 may play a role in the control of endometrial uNK cell function or proliferation.

A comparison of intrauterine balloon, intrauterine contraceptive device and hyaluronic acid gel in the prevention of adhesion reformation following hysteroscopic surgery for Asherman syndrome: a cohort study ☆

OBJECTIVE To compare the efficacy of intrauterine balloon, intrauterine contraceptive device and hyaluronic acid gel in the prevention of the adhesion reformation after hysteroscopic adhesiolysis for Ashermans syndrome. STUDY DESIGN Retrospective cohort study of 107 women with Ashermans syndrome who were treated with hysteroscopic division of intrauterine adhesions. After hysteroscopic adhesiolysis, 20 patients had intrauterine balloon inserted, 28 patients had intrauterine contraceptive device (IUD) fitted, 18 patients had hyaluronic acid gel instilled into the uterine cavity, and 41 control subjects did not have any of the three additional treatment measures. A second-look hysteroscopy was performed in all cases, and the effect of hysteroscopic adhesiolysis was scored by the American Fertility Society classification system. RESULTS Both the intrauterine balloon group and the IUD group achieved significantly (P<0.001) greater reduction in the adhesion score than that of the hyaluronic acid gel group and control group. The efficacy of the balloon was greater than that of the IUD (P<0.001). There was no significant difference in results between the hyaluronic acid gel group and the control groups. CONCLUSION The insertion of an intrauterine balloon or intrauterine device is more effective than the use of hyaluronic acid gel in the prevention of intra-uterine adhesion reformation.

Impact of high body mass index on endometrial morphology and function in the peri-implantation period in women with recurrent miscarriage.

There is evidence that women with a high body mass index may have a higher risk of miscarriage. It is not known if this is due to an endometrial or embryo defect. The aim of this retrospective study was to examine markers of endometrial function in overweight and obese women with recurrent unexplained miscarriage. A total of 136 women were included in the study and classified according to their body mass index (BMI) into two groups, normal BMI (< 25 kg/m(2), n = 70) and high BMI (> or = 25 kg/m(2), n = 66). Endometrial morphology was examined in all patients. A subgroup of 28 patients was examined for endometrial oestrogen and progesterone receptors in different components of the endometrium, and in a further subgroup of 28 patients, endometrial glandular leukaemia inhibitory factor and leukocyte populations were examined. A modest increase in the BMI (30.4 +/- 0.71 kg/m(2)) does not have a significant impact on endometrial steroid receptors, leukocyte populations or endometrial morphology. However, there was a significant negative correlation between endometrial glandular leukaemia inhibitory factor concentrations and the BMI (r = -0.4, P = 0.02), warranting further investigation in prospective studies that include patients with higher BMI levels.