Masako Kuroda

Histological assessment of impact of ovarian endometrioma and laparoscopic cystectomy on ovarian reserve

Aim:  The rate of oocyte decline follows a biphasic pattern, characterized by acceleration between 32 and 38 years old. Ovarian reserve is also affected by external factors, including ovarian disease and iatrogenic damage. The aim of this study was to histologically evaluate the impact of ovarian endometriomas, laparoscopic cystectomy, and age on follicle reserve in healthy ovarian tissues and in surgically resected cyst walls.

Induction of 11β-HSD 1 and Activation of Distinct Mineralocorticoid Receptor- and Glucocorticoid Receptor-Dependent Gene Networks in Decidualizing Human Endometrial Stromal Cells

The actions of glucocorticoids at the feto-maternal interface are not well understood. Here, we show that decidualization of human endometrial stromal cells (HESCs) in response to progesterone and cAMP signaling is associated with a strong induction of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) expression and enzyme activity. Decidualization also triggered a gradual decrease in glucocorticoid receptor (GR) expression and reciprocal increase in mineralocorticoid receptor (MR) levels. Gene expression profiling of differentiating HESCs after small interfering RNA (siRNA)-mediated knockdown of either GR or MR identified 239 and 167 significantly regulated genes, respectively. Interestingly, GR-repressed genes were enriched for Krüppel-associated box domain containing zinc-finger proteins, transcriptional repressors involved in heterochromatin formation. In agreement, GR knockdown was sufficient to enhance trimethylated H3K9 levels in decidualizing cells. Conversely, we identified several MR-dependent genes implicated in lipid droplet biogenesis and retinoid metabolism. For example, the induction in differentiating HESCs of DHRS3, encoding a highly conserved enzyme that catalyzes the oxidation/reduction of retinoids and steroids, was enhanced by aldosterone, attenuated in response to MR knockdown, and abolished upon treatment with the MR antagonist RU26752. Furthermore, we demonstrate that decidualization is associated with dynamic changes in the abundance and distribution of cytoplasmic lipid droplets, the formation of which was blocked by RU26752. In summary, progesterone drives local cortisol biosynthesis by decidual cells through induction of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), leading to transcriptional regulation of distinct GR and MR gene networks involved in epigenetic programming and lipid and retinoid metabolism, respectively.

Strategy for Laparoscopic Cervical Myomectomy

OBJECTIVE Myoma of the uterine cervix is rare, accounting for about 5% of all myomas. Compared with myomas that occur in the uterine corpus, cervical myomas are closer to other organs such as the bladder, ureter, and rectum, and the approach needs to be modified because the organs that have to be considered differ depending on the location of the myoma. We divided cervical myomas into 2 types according to location, comprising an intracervical type and extracervical types. A clear outline of surgical treatment for cervical myoma has not described in previous papers. We then investigated the surgical strategy for these types. PATIENTS Subjects comprised 16 patients who were diagnosed with cervical myoma in our hospital between January 2005 and April 2009, and who underwent laparoscopic myomectomy. RESULT Mean operative time was 105.8 + or - 43.2 (82.8-128.8) min, mean blood loss was 105 + or - 117 (42.6-167.4) ml, and mean specimen weight was 208.3 + or - 195.4 (99.3-306.2) g. Histopathological examination showed atypical myoma in 1 case and leiomyoma in others. CONCLUSIONS 16 cases of cervical myomectomy were performed safely by developing a uniform strategy that uses a fixed operative procedure, even with laparotomy, if sufficient attention is paid to the following 6 points: 1) attempting to reduce the size of the myoma with the use of preoperative GnRH; 2) determining the positional relationship between the myoma and surrounding organs; 3) temporarily blocking uterine artery blood flow with the use of vessel clips; 4) suppressing bleeding during myomectomy with the use of vasopressin; 5) minimizing the risk of damaging surrounding organs by positioning the incision in the myometrium somewhat lateral to the uterine corpus; and 6) the bottom of the wound after enculation should be pulled up by the forceps for suturing to avoid making dead space.

Assessment of tubal disorder as a risk factor for repeat ectopic pregnancy after laparoscopic surgery for tubal pregnancy.

Heading Aims:  We evaluated tubal disorders, including peritubal adhesions, as risk factors for repeat ectopic pregnancy (REP) after laparoscopic linear salpingotomy (LS) or salpingectomy for tubal pregnancy.

The impact of endometriosis, endometrioma and ovarian cystectomy on assisted reproductive technology

PurposeTo assess outcomes in assisted reproductive technology (ART) in infertile women with endometriosis with respect to their concomitant endometrioma status and surgical history in our department.MethodsThis is a retrospective case control study which analyzes informational data obtained at a university hospital. The study drew from a patient pool of 332 cases (877 cIVF/ICSI cycles) that took place in our department from 2006 to 2008. Sixty-one cases (97 cycles) had major indications for cIVF/ICSI with endometriosis. We classified groups from these 61 cases as follows: an unoperated endometrioma group (A) with 31 cycles, a postoperative endometrioma group (B) with 51 cycles, and a no endometrioma group (C) with 15 cycles. We analyzed and compared these three groups and also included a non-endometriosis tubal infertility group (D) with 27 cycles.ResultsIn the control group (D), serum FSH levels and the cancellation rates were significantly lower than those of other groups, and the number of developing follicles was higher. E2 levels before oocyte aspiration in the postoperative endometrioma group (B) was lower. Implantation, pregnancy, delivery and miscarriage rates were not significantly different among the four groups.ConclusionThe results suggest that endometriosis causes a decrease in endocrinologic ovarian function whether or not an endometrioma is also present. As for E2 level before oocyte aspiration, our results suggest that ovarian reserves might be reduced by endometrioma excision, but this is difficult to evaluate. In the endometriosis groups, cancellation rates were significantly higher, although when embryos were transferred the pregnancy rates were not significantly different when compared with the non-endometriosis group. As for infertile women with endometriomas, our results suggest that preexisting ovarian reserve is reduced by the presence of endometriosis, and ovarian reserve might also be reduced by excision of endometriomas.

Vascular density of peritoneal endometriosis using narrow-band imaging system and vascular analysis software.

A pilot study was designed to analyze the vascular density of peritoneal endometriosis in 3 groups of lesions (red, black, and white) in 23 patients with peritoneal endometriosis who underwent laparoscopic surgery using the narrow-band imaging system and vascular analysis software. In the peritoneum, 21 red lesions were present in 10 patients, 12 black lesions were present in 9 patients, 12 white lesions were present in 8 patients, and 2 types of lesion were concomitantly present in 4 patients. Median vascular density of red, black, and white lesions under conventional light was 60.3%, 62.3%, and 60.6%, respectively, and under narrow-band light was 64.4%, 61.5%, and 62.0%, respectively, showing no significant differences among the lesions under either conventional or narrow-band light (p=.71 and p=.84, respectively). The median difference in vascular density under narrow-band and conventional light was not significantly different in black lesions (0.8%) or white lesions (1.0%); however, a difference of 4.5% was noted for red lesions (p <.001). We conclude that red lesions are indicative of early-stage endometriosis with angiogenesis. Use of the narrow-band system and vascular analysis software can enable accurate, objective, and reproducible evaluation of vascular density.

Peritoneal Vascular Density Assessment Using Narrow-Band Imaging and Vascular Analysis Software, and Cytokine Analysis in Women with and without Endometriosis

The development and onset of endometriosis is associated with angiogenesis and angiogenic factors including cytokines. We analyzed intrapelvic conditions in women with endometriosis via vascular density assessment of grossly normal peritoneum and determination of cytokine levels in peritoneal fluid. Seventy-three patients underwent laparoscopic surgery because of gynecologic disease including endometriosis in our department using a narrow-band imaging system. Each patient was analyzed for peritoneal vascular density using commercially available vascular analysis software (SolemioENDO ProStudy; Olympus Corp, Tokyo, Japan). Each patient was also subjected to analysis of interleukin 6 (IL-6), IL-8, tumor necrosis factor-alpha, and vascular endothelial growth factor concentrations in peritoneal fluid. We defined 4 groups as follows: group 1, endometriosis: gonadotropin-releasing hormone (GnRH) agonist administration group (n=27); group 2, endometriosis: GnRH agonist nonadministration group (n=15); group 3, no endometriosis: GnRH agonist administration group (n=18); and group 4, no endometriosis: GnRH agonist nonadministration group (n=13). No significant differences in peritoneal vascular density between the 4 groups were found under conventional light; however, under narrow-band light, vascular density in the endometriosis groups (groups 1 and 2) was significantly higher. Cytokine analysis of the 4 groups determined that IL-6 and IL-8 concentrations were significantly higher compared with the no endometriosis groups (groups 3 and 4). Tumor necrosis factor-alpha and vascular endothelial growth factor concentrations were not significantly different between groups. In endometriosis, peritoneal vascular density was significantly higher as assessed using the narrow-band imaging system and SolemioENDO ProStudy, whereas GnRH agonist did not obviously decrease vascular density but IL-6 concentration was lower in the GnRH agonist administration group.

Cytogenetic analysis of the retained products of conception after missed abortion following blastocyst transfer: a retrospective, large-scale, single-centre study

Cytogenetic analysis of the retained products of conception (POC) is the most effective test for identifying miscarriage causes. However, there has been no large-scale study limited to blastocyst transfer. This study retrospectively reports the findings of 1030 cases in which POC analysis was performed after missed abortion following single blastocyst transfer performed at the Shinbashi Yume Clinic. We identified 19.4% as normal karyotypes and 80.6% as aneuploid. These cases broke down into: 62.3% trisomy; 7.8% double trisomy; 0.5% triple or quadruple trisomy; 1.3% monosomy 21; 3.2% monosomy X; 0.1% 47,XXY; 1.0% polyploidy; 1.0% mixed; 1.1% embryonic mosaicism; and 2.4% structural anomalies. In samples with normal karyotypes, 49.5% were female while 50.5% were male. The occurrence of trisomy and double trisomy were both significantly more frequent in the ≥38 years group than in the ≤37 years group (P < 0.01). Trisomy was significantly more frequently associated with fetal heartbeat (P < 0.01); double trisomy, polyploidy and normal karyotype were significantly more frequent with no fetal heartbeat (P < 0.01). There was no significant difference in the frequency of chromosomal abnormalities between the number of miscarriages or blastocyst quality. Thus, POC cytogenetic testing is highly valuable for ascertaining the cause of miscarriage.

Surgery-assisted reproductive technology hybrid therapy: a reproductive procedure for an infertile woman of late reproductive age with multiple myomas.

Aim:  To produce a successful pregnancy in a 38‐year‐old infertile patient with relapsed myoma using a technique we refer to as ‘surgery‐assisted reproductive technology (ART) hybrid therapy’ because it combines ART for cryopreservation of in vitro fertilized eggs with reproductive surgery.

Levothyroxine supplementation improves serum anti‐Müllerian hormone levels in infertile patients with Hashimoto’s thyroiditis

Thyroid dysfunction and autoimmunity are associated with an adverse effect on fertility. An aberrant high thyroid stimulating hormone level is associated with diminished ovarian reserve in women of reproductive age; however, the utility of levothyroxine (LT4) replacement for infertile patients with subclinical hypothyroidism is still under discussion. The aim of this study was to investigate whether LT4 supplementation for infertile patients with subclinical hypothyroidism improves impaired ovarian function.