Intrauterine adhesion after hysteroscopic myomectomy of submucous myomas.

PURPOSE: To evaluate the frequency of intrauterine adhesion (IUA) after hysteroscopic myomectomy, and to analyze the association of IUA and the location of submucous myomas and the use of postoperative barrier (POB). METHODS: Hysteroscopic myomectomy was performed in 217 patients with submucous myomas. The retrospective investigation was performed, and the cases were divided into three groups: cases with solitary submucous myoma (SSM; group 1), cases with apposing submucous myomas (ASMs; group 2) and cases with submucous myomas that were far from each other or not in apposition to one another (not apposing submucous myomas: NASMs; group 3). As POB, intrauterine device with oxidized regenerated cellulose and silicon sheet was inserted immediately after surgery. RESULTS: IUA formation after hysteroscopic myomectomy was more frequent in group 2 than groups 1 and 3 (p = 0.03 and 0.01, respectively), despite the higher rates of POB use (p = 0.02). There was no significant difference in IUA formation in cases with POB between each group (p = 0.06 and 0.21, respectively). But in cases without POB, group 2 showed higher rates of IUA formation than group 1 (p = 0.04) and group 3 (p = 0.03). Multivariable analysis for IUA formation demonstrated that ASMs were a risk factor of IUA (hazard ratio [HR] = 27.9, p < 0.01), and the use of POB was a prognostic factor for reduction of IUA formation (HR = 0.08, p < 0.01). CONCLUSION: ASMs appear to be a risk factor for IUA formation. The use of POB may be associated with preventing IUA formation after hysteroscopic myomectomy.

Efficacy of silicone sheet as a personalized barrier for preventing adhesion reformation after hysteroscopic adhesiolysis of intrauterine adhesions.

PURPOSE: To evaluate the efficacy of silicone sheet as a new type of barrier for preventing adhesion reformation following hysteroscopic adhesiolysis of intrauterine adhesions (IUAs). METHODS: Hysteroscopic adhesiolysis was performed for 36 patients with IUAs. The adhesion reformation rate was retrospectively compared between 26 patients treated with silicone sheet (group 1) and 10 patients treated with an intrauterine device wrapped in oxidized regenerated cellulose as a barrier (group 2). For patients in group 1, a 1-mm-thick silicone sheet was cut to fit the size and shape of the individual uterine cavity as a personalized barrier. RESULTS: The size and shape of each silicone sheet used for patients in group 1 differed significantly. The adhesion reformation rate was significantly lower in group 1 (4/26, 15.4%) than in group 2 (4/10, 40.0%; P = 0.03), although the pregnancy rate (14/20, 70.0% vs. 5/10, 50.0%; P = 0.28) and miscarriage rate (2/14, 14.3% vs. 1/5, 20.0%; P = 0.72) were not significantly different. CONCLUSION: Use of silicone sheets appears to be effective for preventing adhesion reformation following hysteroscopic adhesiolysis of IUAs. This is the first study to investigate the efficacy of silicone sheet used as a personalized barrier for preventing IUAs.

Role of dilatation and curettage performed for spontaneous or induced abortion in the etiology of endometrial thinning.

AIM: The aim of this study was to clarify the role of dilatation and curettage (D&C) performed for spontaneous or induced abortion in the etiology of endometrial thinning. METHODS: This was a retrospective and cross-sectional study of 310 infertile patients from January 2013 through December 2015. Endometrial thickness observed 5-7 days after ovulation in a natural menstrual cycle was correlated with the number of D&C noted in each patient's history. RESULTS: Study 1 was an investigation of patients without D&C (group A: n = 232) and patients with D&C performed for spontaneous abortion (group B: n = 46). Study 2 was an investigation of patients in group A and patients with D&C performed for induced abortion (group C: n = 32). A significant negative correlation (P < 0.01) between endometrial thickness and number of D&C was observed in both studies. The mean endometrial thickness of the patients in group A was 10.9 ± 2.1 mm. The mean endometrial thickness of the patients in group B with one and ≥two D&C was 7.9 ± 2.3 and 6.9 ± 2.9 mm, respectively. The mean endometrial thickness of the patients in group C with one and ≥two D&C was 9.1 ± 2.3 and 7.8 ± 2.0 mm, respectively. There was a tendency toward gradual endometrial thinning following repeated procedures and the number of previous D&C was significantly associated with endometrial thinning (P < 0.001) in both studies. CONCLUSION: D&C performed for spontaneous or induced abortion may play a causal role in endometrial thinning.

A remarkably easy knot-tying technique for single-incision laparoscopic surgery with the SILS port for gynecologic diseases.

Single-incision laparoscopic surgery (SILS) has been quickly accepted, especially for women, because the cosmetic benefits may be greater than with ordinary laparoscopic surgery. In gynecologic disease, SILS is appropriate for diagnostic laparoscopy, oophorectomy, and salpingectomy, among other conditions. In addition, the knot-tying process for intracorporeal suturing during SILS is a major rate-limiting step and a key determinant of the popularity of SILS. Although a roticulator instrument is useful for creating the needed operative angle, knot tying is still believed to be difficult. We have devised a remarkably simple knot-tying technique that can be applied during SILS with a SILS Port with a Roticulator and a straight-type needle driver. We determined that, after transfixing the needle, the long tail of the thread should be grasped at around 90 degrees relative to the long axis of tip of the Roticulator, which is articulated at 80 degrees. This automatically forms an ideal C-loop because of gravitation. The needle attached to the long tail should face the distal side from the tip of Roticulator (from the surgeon's perspective). The apex of the C-loop is then toward the proximal side from the tip of the Roticulator (from the perspective of the surgeon). This thread position is important during the knot-tying process. The upper arm of the C-loop should then be entwined by applying a series of axial spinning movements to the rod of the needle driver. At this time, the jaws of the needle driver should be kept open so the thread does not slip off of the rod. The benefit of this technique is that it does not require any special skills; any surgeon able to perform intracorporeal suturing should also be able to easily tie knots during SILS.

Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats.

BACKGROUND: Zucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance. METHODS: In this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7). RESULTS: Ovaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks) and androstenedione (all weeks) than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats. CONCLUSIONS: Our findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats.

Altered expression of Fas/Fas ligand/caspase 8 and membrane type 1-matrix metalloproteinase in atretic follicles within dehydroepiandrosterone-induced polycystic ovaries in rats.

One of the characteristics of polycystic ovary syndrome (PCOS) is the presence of cystic follicles in various stages of growth and atresia, the latter of which is known to be the result of apoptosis and tissue remodeling. To further investigate the process of follicular atresia, we compared ovarian expression and localization of Fas, Fas ligand (FasL), casapse-8 and membrane-type1 matrix metalloproteinase (MT1-MMP) in rats treated with dehydroepiandrosterone (DHEA) as a model of PCOS, and in control rats. We found that the numbers of TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive follicles were significantly higher in ovaries from PCOS rats than in those from control rats (P < 0.05), as were ovarian levels of FasL mRNA and protein, processed caspase-8 protein and MT1-MMP mRNA. Correspondingly, we also observed an increase in the level of MTI-MMP catalytic activity and a decrease in the level of pro-caspase-8 protein. In addition, immunohistochemical analyses showed that MT1-MMP and FasL co-localize with TUNEL-positive apoptotic granulosa cells within atretic follicles of PCOS ovaries. Our results suggest that under the PCOS-like conditions induced by DHEA, the Fas/FasL/Caspase-8 (death receptor dependent) pathway is pivotal for follicular atresia, and that increased levels of MT1-MMP likely play an important role in tissue remodeling during structural luteolysis.

Significance of matrix metalloproteinases in the pathophysiology of the ovary and uterus.

Matrix metalloproteinases (MMP) are capable of degrading a variety of extracellular matrix (ECM) proteins and are also involved in the processing of a number of bioactive molecules. Our findings indicate that the functions of MMP in the ovary and uterus are organ-specific and time-dependently vary during the reproductive cycle. Prolactin induces structural luteolysis indicated by loss of luteal weight, protein and DNA within 36 h after pretreatment with ergot alkaloid. MMP activation appears crucial for the selective depletion of protein during luteal involution, which entails loss of ECM accompanied by apoptosis. During GnRHagonist-induced luteolysis, this response was also associated with marked increases in MMP-2, which degraded collagen type IV, and MT1-MMP, which in addition to activating MMP-2 also degrades collagen type I, III and V. We also found that the level of MT1-MMP and MMP-2 expression in the human CL is greater during the late luteal phase than during either the early mid luteal phases or during gestation, respectively. That dehydroepiandrosterone (DHEA) treatment caused the formation of cysts from antral follicles in the ovaries of immature rats while depressing MMP-2 collagenolytic activity and enhancing lysyl oxidase expression highlights the importance of collagen degradation in the process of ovulation and suggests that changes in the activities of these enzymes play a key role in ovarian cystogenesis in polycystic ovary syndrome patients. Furthermore, immunohistochemical analyses showed that MT1-MMP and FasL co-localize with TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive apoptotic granulosa cells in rats treated with DHEA, that the Fas/FasL/Caspase-8 (death receptor-dependent) pathway is pivotal for follicular atresia and that increased levels of MT1-MMP likely play an important role in tissue remodeling during follicular atresia. After parturition, the uterus undergoes involution, a conspicuous feature characterized by a rapid reduction in the collagen content mediated by degradation of extracellular collagen bundles. Our findings strongly suggest that MT1-MMP, MMP-2 and MMP-9 are each time-dependently regulated and play important roles in tissue remodeling during postpartum uterine involution. (Reprod Med Biol 2006; 5: 235-243).

Identical changes in Bax expression, but not Fas ligand expression, occur in structural luteolysis in gonadotropin releasing hormone agonist- and prolactin-treated superovulated rats.

Structural luteolysis induced by gonadotropin releasing hormone agonist (GnRHa) or prolactin (PRL) is defined as histological involution of the corpus luteum. We reported that one of the mechanisms of structural luteolysis induced by PRL was tissue remodeling by matrix metalloproteinase (MMP) and also apoptosis in superovulated rats. We also reported that GnRHa induced structural luteolysis with elevation of MMP. In this study, we investigated whether GnRHa caused apoptosis in mature corpus luteum of superovulated rats and also examined the expression of apoptosis-related molecules (Fas, Fas ligand (FasL), Bcl-2, Bax). We gave 4-day GnRHa treatment 5 days after hCG injection to immature female rats treated with pregnant mare surum gonadotrophin (PMSG) and hCG to induce structural involution of mature corpus luteum. PMSG-hCG-treated rats without GnRHa treatment, rats treated with bromocryptine (Brom) to induce functional luteolysis and rats treated with Brom followed by PRL (Brom+PRL) to mimic the PRL surge to induce structural luteolysis as we previously reported were used for comparison. GnRHa treatment caused structural luteolysis characterized by structural involution, a decrease in the serum progestin level, and apoptotic bodies as well as structural luteolysis induced by Brom+PRL. FasL expression in corpora lutea was elevated after Brom treatment, but there was no elevation of FasL after GnRHa treatment started. FasL expression decreased and Bax expression increased in structural luteolysis induced by GnRHa as well as Brom+PRL treatment, although Fas and Bcl-2 expression did not change throughout the luteal phase. In summary, both GnRHa and Brom+PRL caused structural luteolysis, one of whose mechanisms was apoptosis with an increase in Bax expression, but not with an identical change in FasL expression. It is speculated that the significance in alteration of FasL may involve some mechanism other than apoptosis.

The significance of membrane type 1 metalloproteinase in structural involution of human corpora lutea.

The expression of membrane type 1 (MT1) matrix metalloproteinase (MMP), MMP-2, and tissue inhibitors of MMP-1 and -2 during structural involution of the human corpus luteum was examined using immunohistochemistry, Northern blotting, Western blotting, gelatin zymography and in-situ hybridization techniques. The corpora lutea of 20 patients were investigated at the time of total hysterectomy and were obtained from five patients each in the early, mid- and late luteal phases and during gestation. Immunohistochemistry for MT1-MMP in corpus luteum showed that the protein appeared in granulosa lutein cells in the late luteal phase. Both the expression of MT1-MMP mRNA and the amount of the protein increased in the late luteal phase. In-situ hybridization showed that MT1-MMP mRNA was localized mainly in the cytoplasm of granulosa lutein cells. These results suggest that increased expression of MT1-MMP may be a major factor in remodelling of the human corpus luteum during structural luteolysis.