Retrospective cohort study of the risk factors for secondary infertility following hysteroscopic metroplasty of the uterine septum in women with recurrent pregnancy loss.

Purpose: A hysteroscopic metroplasty was performed for women with recurrent pregnancy loss owing to a uterine septum, following which some women became infertile. The aim of this study was to elucidate the risk factors of secondary infertility 1 year after hysteroscopic metroplasty for a uterine septum. Methods: A retrospective, single-center, cohort study included women with a history of at least two miscarriages that had been attributed to a uterine septum who underwent a hysteroscopic metroplasty. The patients' background data were compared between the patients who conceived and those who remained infertile at 1 year postoperatively. The data were analyzed by using the Mann-Whitney U-test and multivariate analyses. Results: The postoperative live birth rate was 83.9% (n = 26), with persistent infertility in five women at 1 year. When comparing the pregnancy group with the infertile group, the women in the postoperative infertility group were significantly older than those in the postoperative pregnancy group. The multivariate analysis showed that age was an independent risk factor for persistent infertility. Conclusion: Age was identified as an independent risk factor for postoperative secondary infertility. Therefore, surgery as early as possible is recommended.

Gonadotropin regulation and role of ovarian osteopontin in the periovulatory period.

Osteopontin (OPN), a secreted glycoprotein, has multiple physiological functions. This study investigated the regulation and roles of OPN in the mouse ovary during the periovulatory stages. Immature female mice were treated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) to simulate follicle maturation and ovulation. In situ hybridization and real-time RT-PCR were performed to assess expression of Opn in the periovulatory ovary. Granulosa cells (GCs) from PMSG-primed immature mice were cultured with or without hCG in the presence or absence of OPN, and effects on expression of Opn, progesterone synthesis, and vascular endothelial growth factor (VEGF) signaling were assessed by real-time RT-PCR, ELISA, and western blotting analysis. Opn transcripts were significantly upregulated 3 h after hCG treatment, followed by a peak at 16 h, and the transcripts localized to GCs. Incubation with hCG significantly increased quantities of Opn transcripts in GCs and OPN levels in the culture medium at 12 and 24 h. Furthermore, OPN treatment caused a significant increase in the levels of Star protein, P 450 cholesterol side-chain cleavage enzyme (p450scc), 3-beta-hydroxysteroid dehydrogenase (Hsd3b), and progesterone in the culture medium. OPN treatment promoted Vegf expression in GCs, which was significantly suppressed by a phosphoinositide 3-kinase (PI3K) inhibitor. In addition, OPN treatment stimulated phosphorylation of AKT, a downstream PI3K signaling molecule. In conclusion, expression of Opn was upregulated in mouse ovarian GCs in response to a gonadotropin surge through epidermal growth factor receptor signaling, which enhances progesterone synthesis and Vegf expression during the early-luteal phase.

Recurrence of ovarian endometrioma after laparoscopic excision: risk factors and prevention.

AIM: The aim of this study was to assess the cut-off age of the risk factors for postoperative recurrence of ovarian endometriomas and to evaluate the end-points of follow-up after laparoscopic excision of ovarian endometriomas. MATERIAL AND METHODS: We retrospectively reviewed 167 patients who underwent laparoscopic excision of ovarian endometriomas at our hospital between 2000 and 2009, and followed up the patients until 2010. Following surgery, patients chose to receive gonadotrophin-releasing hormone agonist, oral contraceptive pills (OCP), dienogest, or no medication and underwent regular ultrasonographic examinations. Potential risk factors for recurrence, including age at surgery, were assessed in the patients receiving no medication. Postoperative recurrence, defined as re-appearance of an ovarian endometrioma > 2 cm in size, was assessed for each treatment group. RESULTS: Age at surgery was the only significant risk factor for recurrence, at a cut-off of 32 years, obtained through receiver-operator curve analysis. In patients not receiving medication, the recurrence rate gradually increased up to 50% over 5 years; there was no recurrence 5 years after surgery. Although no recurrence was seen in patients during continuous treatment with OCP or dienogest, the disease recurred in 55.5% of patients after discontinuing OCP. CONCLUSIONS: Although adjuvant therapy for all patients may represent overtreatment, the findings of the present study suggest that, in the interest of fertility preservation, continuous postoperative hormonal treatment should be administered, at least to patients younger than 32 years. In patients who decline hormonal treatment, we recommend that they undergo follow-up for recurrence until 5 years after surgery.

Changing our view of minimally invasive gynecologic surgery: a review of laparoendoscopic single-site surgery and a report on new approaches.

The recent emergence of laparoendoscopic single-site surgery (LESS) has had a great impact on gynecology. As LESS grows in popularity, attention has been paid to the procedure's cosmetic benefits. Although in theory LESS is an ideal approach that leaves no visible scars and improves patients' quality of life, the outcomes are not always ideal according to recently published data. Therefore, alternative approaches, such as mini-laparoscopy, are also becoming more popular. Herein, we review randomized trials studying the benefits of LESS in gynecology and discuss alternative approaches. Finally, we propose the mimic approach as the next generation for non-visible scar surgery.

Mimic mini-laparoscopic surgery is a simple and secure approach using direct placement of 3-mm trocars without noticeable scars.

Minimally invasive surgery is widely used in gynecology. Women who seek a cosmetic advantage (i.e., concealed scars) choose minimally invasive surgery. Although laparoendoscopic single-site surgery could be an ideal solution, some of our patients have had cosmetic problems, such as pigmentation and cicatrix of the umbilicus. In addition, umbilical eversion and umbilical herniation occasionally develop. Therefore, mini-laparoscopic surgery using 3-mm trocars can be recommended for patients who do not want the natural appearance of the navel to be altered. We have developed an approach to achieve a superior cosmetic outcome by direct placement of 3-mm trocars in the lateral wall of the abdomen and at the lower border of the pubic hair. We refer to this method as mimic mini-laparoscopic surgery and report cases in which this procedure was used.

Novel hybrid laparoscopic sacrocolpopexy for pelvic organ prolapse with a severe paravaginal defect.

Abdominal sacrocolpopexy is the gold standard for treating pelvic organ prolapse (POP) because of safety and durable good results. More recently laparoscopic sacrocolpopexy (LSC), a less invasive approach, has become popular. Although these surgeries are versatile and can treat almost all patients with POP, these techniques have shortcomings. Specifically, reinforcement of lateral vaginal defects are not very strong, thus patients with POP and a severe paravaginal defect are not good candidates for abdominal or laparoscopic sacrocolpopexy. To overcome this problem, we developed a novel type of LSC, which can reinforce severe paravaginal defects by using a reversed T-shaped anterior mesh combining the advantage of transvaginal mesh surgery. We refer to this novel surgery as 'hybrid LSC'. Thus far, eight patients have successfully undergone this surgery. Hybrid LSC is a simple and secure method, and is an alternative treatment for POP with a severe paravaginal defect.

Rapid and transient upregulation of CCL11 (eotaxin-1) in mouse ovary during terminal stages of follicular development.

PROBLEM: This study aimed to investigate the regulation of expression, localization and physiological role of the CCL11/CCR3 axis in mouse ovary during the periovulatory period. METHOD OF STUDY: CCL11/CCR3 expression in the mouse ovary after treatment with pregnant mare serum gonadotropin (PMSG) followed by human chorionic gonadotropin (hCG) 48 hr later was assessed in vivo and in 3-dimensional cultures in vitro. RESULTS: Real-time RT-PCR analyses revealed transient CCL11 mRNA upregulation 6 hr after hCG treatment. Immunohistochemical staining of serial ovarian sections demonstrated overlapping expression of CCL11, CCR3 and CD31 endothelial cell marker in the theca-interstitial layer at 10 hr after hCG treatment. In vitro 3-dimensional cultures of periovulatory ovarian tissues demonstrated that treatment with anti-CCL11 neutralizing antibody significantly decreased CD31 transcript. CONCLUSIONS: Gonadotropin surge leads to transient CCL11/CCR3 axis upregulation in the ovarian theca-interstitial layer, suggesting that it is involved in periovulatory physiological processes by affecting follicular vessels.

Novel hybrid mesh surgery combines sacrocolpopexy with transvaginal mesh placement for pelvic organ prolapse.

Mesh surgeries, such as sacrocolpopexy and transvaginal mesh surgery, are commonly used to treat pelvic organ prolapse. Although mesh surgeries have a high success rate, they are unsuitable for some patients. For a patient with pelvic organ prolapse and highly calcified multiple fibroids, we performed hybrid sacrocolpopexy combined with transvaginal mesh surgery with a method modified for the patient's condition. Three months after surgery, the results were highly satisfactory. This approach is simple, secure, and versatile for patients who are not good candidates for conventional mesh surgeries. This novel hybrid mesh surgery is an option for treating various types of pelvic organ prolapse.

Proteomic analyses of recombinant human follicle-stimulating hormone and urinary-derived gonadotropin preparations.

OBJECTIVE: To understand the properties of each available gonadotropin preparation, especially in terms of the differences between urinary-derived and recombinant preparations. STUDY DESIGN: Human menopausal gonadotropin (hMG), highly purified urinary-derived follicle-stimulating hormone (uFSH-HP) and recombinant FSH (rFSH) were subjected to 2-dimensional gel electrophoresis (2-DE), and protein spots were visualized by silver-staining procedures. Major spots were analyzed by mass spectrometry. Fluorescent-labeled preparations were also subjected to 2-DE to evaluate the quantities of FSH isohormones contained in each preparation. RESULTS: 2-DE and mass spectrometry analyses of hMG identified many extracellular proteins as major impurities and several plasma membrane proteins including prion proteins. Both uFSH-HP and rFSH demonstrated slight impurities and showed several alpha and beta subunit isohormones. rFSH contained higher amounts of the basic isohormones of the alpha subunit than uFSH-HP, whereas the predominance of the basic isohormones was less significant in the beta subunit. CONCLUSION: Proteomic analyses demonstrated the detailed protein profiles of each preparation. Differences in the quantities of alpha subunit isohormones may contribute to the variations in FSH activity observed between recombinant and urinary-derived FSH preparations.

Efficacy of long-term, low-dose gonadotropin-releasing hormone agonist therapy (draw-back therapy) for adenomyosis.

BACKGROUND: The usefulness of long-term, low-dose gonadotropin-releasing hormone agonist (GnRHa; buserelin acetate) therapy, so-called draw-back therapy, for the treatment of adenomyosis was investigated not. MATERIAL/METHODS: A retrospective observational study was conducted covering the period between January 2003 and March 2008. The subjects consisted of 12 patients with adenomyosis who underwent draw-back therapy for 2 years and had previously received GnRHa. GnRHa was initiated at 900 microg/day (6 nasal sprays/day). When the CA-125 level normalized, the GnRHa dosage was adjusted to 150-750 microg/day to achieve a plasma estradiol (E2) concentration of 20-50 pg/ml (i.e., the therapeutic window). Pain during withdrawal bleeding and chronic pelvic pain were assessed using a visual analogue scale. In addition, bone mineral density (BMD) of the lumbar vertebrae was measured using dual-energy X-ray absorptiometry. RESULTS: The mean GnRHa dose during draw-back therapy was 435 microg/day (2.9 nasal sprays/day). The mean E2 level during draw-back therapy was 36.3+/-14.3 pg/ml. The intensity of chronic pelvic pain was significantly lower during draw-back therapy than before draw-back therapy, and was nearly eliminated in many patients (4.8+/-1.2 vs. 0.6+/-0.7, respectively [p=0.000]). Compared to the severity of vasomotor symptoms during previous regular GnRHa therapy, the severity of vasomotor symptoms during draw-back therapy was significantly lower (3.8+/-0.7 vs 1.1+/-0.7, respectively [p=0.000]). The decrease in BMD during a 6-month course of treatment was 0.96+/-0.9%. CONCLUSIONS: GnRHa draw-back therapy allowed maintenance of plasma E2 levels within the therapeutic window. GnRHa can thus be administered for long periods of time while maintaining therapeutic effects on adenomyosis and suppressing adverse events.