Efficacy and safety of newly developed ganirelix acetate in infertile women for assisted reproductive technology: a prospective, randomised, controlled study.

This study aimed to investigate the efficacy of Ganilever pre-filled syringe (PFS), a newly developed ganirelix acetate, for the inhibition of premature luteinising hormone (LH) surge in in vitro fertilisation (IVF). A prospective randomised controlled study was conducted (NCT03051087). A total of 236 women (Ganilever group: 114, Orgalutran group: 122) were finally analysed. The patients with LH of >10 mIU/mL on the day of human chorionic gonadotropin (hCG) injection were 0 (0.0%) and 3 (2.5%) in the Ganilever and Orgalutran groups, respectively (p= .25). The number of retrieved oocytes from two groups did not show any significant difference (12.0 ± 6.4 vs. 11.8 ± 6.3, p= .73). Furthermore, the two groups did not show significant differences in the number of good-quality oocytes and embryo, and the rate of fertilisation. Similar safety profiles were also observed. In conclusion, Ganilever PFS showed comparable IVF outcomes and safety profile in IVF, as compared to the Orgalutran. Impact StatementWhat is already known on this subject? Premature LH surge during controlled ovarian stimulation results in the induction of luteinisation of the immature follicles. Thus, gonadotrophin-releasing hormone (GnRH) antagonist protocol was suggested as an option for suppression of premature LH surge. Currently, one of GnRH antagonists being widely used is ganirelix acetate (Orgalutran®; Organon, Oss, The Netherlands). Ganilever pre-filled syringe (PFS) is a newly developed GnRH antagonist containing ganirelix acetate as an active ingredient.What do the results of this study add? Our study demonstrated that Ganilever PFS showed comparable IVF outcomes and patient safety profile in infertile women undergoing in IVF-ET, as compared to the Orgalutran.What are the implications of these findings for clinical practice and/or further research? The results of our study will provide another available GnRH antagonist to be used in patients with IVF.

The impact of post-warming culture duration on clinical outcomes of vitrified-warmed single blastocyst transfer cycles.

OBJECTIVE: The objective of the study was to compare the effects of long-term and short-term embryo culture to assess whether there is a correlation between culture duration and clinical outcomes. METHODS: Embryos were divided into two study groups depending on whether their post-warming culture period was long-term (20-24 hours) or short-term (2-4 hours). Embryo morphology was analyzed with a time-lapse monitoring device to estimate the appropriate timing and parameters for evaluating embryos with high implantation potency in both groups. Propensity score matching was performed to adjust the confounding factors across groups. The grades of embryos and blastoceles, morphokinetic parameters, implantation rate, and ongoing pregnancy rate were compared. RESULTS: No significant differences were observed in the implantation rate or ongoing pregnancy rate between the two groups (long-term culture group vs. short-term culture group: 56.3% vs. 67.9%, p=0.182; 47.3% vs. 53.6%, p=0.513). After warming, there were more expanded and hatching/hatched blastocysts in the long-term culture group than in the short-term culture group, but there was no significant between-group difference in embryo grade. Regarding pregnancy outcomes, the time to complete blastocyst re-expansion after warming is shorter in women who became pregnant than in those who did not in both culture groups (long-term: 2.19±0.63 vs. 4.11±0.81 hours, p=0.003; short-term: 1.17±0.29 vs. 1.94±0.76 hours, p=0.018, respectively). CONCLUSION: The outcomes of short-term culture and long-term culture were not significantly different in vitrified-warmed blastocyst transfer. Regardless of the post-warming culture time, the degree of blastocyst re-expansion 3-4 hours after warming is an important marker for embryo selection.

Increased proportion of mature oocytes with sustained-release growth hormone treatment in poor responders: a prospective randomized controlled study.

PURPOSE: Supplementation of growth hormone (GH) during controlled ovarian stimulation (COS) has been suggested to improve ovarian response. Despite potential benefits in poor responders, multiple injections of GH during COS are inconvenient. We conducted a randomized controlled study to evaluate the efficacy and safety of sustained-release human GH in poor responders undergoing in vitro fertilization (IVF). METHODS: This was a single-center, randomized, open-label, parallel study. Infertile women who satisfied the Bologna criteria for poor responders were randomized into GH treatment and control groups. The treatment group received a sustained-release GH (Eutropin Plus® 20 mg) three times before and during COS (mid-luteal, late luteal, and menstrual cycle day 2). The baseline characteristics and IVF outcomes were compared between the two groups. RESULTS: A total of 127 patients were included in the analysis. The mean age was 39.6 years and mean anti-Müllerian hormone level was 0.6 ng/ml. There was no significant difference in the baseline characteristics between GH treatment and control groups. The number of follicles on the human chorionic gonadotropin triggering day (3.1 ± 2.3 vs. 2.4 ± 1.6, P = 0.043) and the proportion of metaphase II oocytes (67.5 vs. 52.3%, P = 0.030) were higher in the GH group than in controls. The percentage of clinical and ongoing pregnancy and miscarriage was not different between the two groups. CONCLUSION: Supplementation of sustained-release GH before and during COS improved ovarian response, with an increase in mature oocytes in poor responders. Further studies are needed to ensure this benefit in general infertility patients.

What is the best treatment of heterotopic cervical pregnancies for a successful pregnancy outcome?

Heterotopic pregnancy is rare event and the risk is increased with assisted reproductive technology procedures. Heterotopic cervical pregnancy is even more unusual. We report a rare case of heterotopic cervical pregnancy that was managed successfully. A 36-year-old women who conceived by IVF-ICSI was diagnosed with heterotopic cervical pregnancy. She visited the emergency room with vaginal bleeding at 5 weeks of gestation and underwent careful intracervical gestational sac reduction with forceps under abdominal guidance the next day. The postoperative course was uneventful and with regular check-ups, the intrauterine pregnancy (IUP) progressed unremarkably through 41 weeks with delivery of a healthy newborn. We reviewed a total of 37 cases of heterotopic pregnancy that have been reported in the English language literature. There have been many attempts to eliminate the cervical embryo while preserving the IUP, and complete cervical evacuation is important in order to avoid infection, bleeding, and premature birth.

Endometrioid adenocarcinoma arising from endometriosis of the uterine cervix: a case report.

Endometrioid adenocarcinoma arising from endometriosis of the uterine cervix is rare in premenopausal woman. We describe here a patient with this condition and review the clinical and pathological features of these tumors. A 48-yr-old woman complaining of severe dysmenorrhea was referred for investigation of a pelvic mass. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Histological examination revealed an endometrioid adenocarcinoma directly adjacent to the endometriosis at the uterine cervix, with a transition observed between endometriosis and endometrioid adenocarcinoma. The patient was diagnosed as having endometrioid adenocarcinoma arising from endometriosis of the uterine cervix and underwent postoperative chemotherapy. Gynecologists and pathologists should be aware of the difficulties associated with a delay in diagnosis of endometrioid adenocarcinoma arising from endometriosis when the tumor presents as a benign looking endometrioma.

Two-port total laparoscopic hysterectomy with a multichannel port.

Total laparoscopic hysterectomy (TLH) is often performed in many countries. TLH has been shown to involve shorter hospital stays, as well as less bleeding and postoperative pain, than conventional abdominal hysterectomy. The skin incision for the laparoscopy is smaller than that of the laparotomy, but multiple incisions may decrease the cosmetic satisfaction of patients. The multiple puncture sites also increase the cost of trocars and trocar-associated complications, such as bleeding, hernias, and wound infection. Therefore, in this paper we introduce a two-port TLH technique with a multichannel port employing the transumbilical one-port technique performed by Ryu et al. To perform a two-port TLH, the ancillary 5-mm trocar was inserted at the left iliac fossa under laparoscopic view. The inserted umbilical trocar was removed and the skin incision was extended about 1.5 cm. An Alexis wound retractor XS (Applied Medical) was inserted through the extended umbilical wound. The wrist portion of a 6 (1/2) rubber glove covered the wound retractor, and two trocars were inserted into the fingers of the glove and ligated with rubber bands. A 5- or 10-mm laparoscope and atraumatic forceps were inserted through the umbilical port. TLH was performed in the usual manner. This two-port method would be cost-effective considering the conventional laparoscopic instruments. The development of multichannel trocars and minimized laparoscopic devices may confer less invasive operative techniques that also cause less scarring.

Loss of hMLH1 expression is associated with less aggressive clinicopathological features in sporadic endometrioid endometrial adenocarcinoma.

AIM: To assess the incidence and clinicopathological significance of microsatellite instability (MSI) and the protein expression of hMLH1 and hMSH2 in sporadic endometrioid endometrial adenocarcinoma (SEEA). METHODS: A total of 50 patients with pure endometrioid sporadic endometrial adenocarcinoma were enrolled in the study. MSI analysis was done using five polymorphic markers (BAT26, D5S346, BAT25, D17S250, D2S123) and the protein expression of the hMLH1 and hMSH2 genes was determined by immunohistochemical staining. MSI was detected in 24% (12/50) of SEEA cases. RESULTS: There was a significant correlation between MSI status and loss of hMLH1, hMSH2 expression, respectively. No significant association was found between MSI status and clinicopathological parameters, including age, grade, stage, depth of myometrial invasion, lymph-vascular space invasion (LVI), lymph node involvement or peritoneal cytology. However, significant correlations were found between loss of hMLH1 and a lower histological grade and the absence of LVI in patients with SEEA. CONCLUSIONS: According to these results, MSI and a loss of protein expression of hMLH1 and hMSH2 may be associated with the pathogenesis of SEEA. In addition, hMLH1 immunostaining might have a role as a prognostic parameter. Further research using a large number of cases is needed to confirm our observations.