Hsing-Tse Yu

Eutopic endometrial interleukin-18 system mRNA and protein expression at the level of endometrial-myometrial interface in adenomyosis patients

OBJECTIVE To investigate the eutopic endometrial interleukin-18 (IL-18) system including interleukin-18 (IL-18), IL-18 receptor (IL-18R), and IL-18 binding protein (IL-18BP), mRNA, and protein expression in patients with adenomyosis. DESIGN A clinical and molecular study. SETTING Clinical and academic research setting in a university medical center. PATIENT(S) Twenty-eight samples of human eutopic endometria were obtained from surgical specimens of normal cycling women undergoing hysterectomy for uterine adenomyosis (n = 19); the control group (n = 9) was women undergoing hysterectomy for benign reason including uterine fibroids. INTERVENTION(S) Quantitative competitive polymerase chain reaction (QC PCR) and immunohistochemistry studies were performed. MAIN OUTCOME MEASUREMENT(S) The differences of the IL-18 system mRNA and the ratio of IL-18BP to IL-18 in the eutopic endometrium of uterine adenomyosis and control group were analyzed. RESULT(S) IL-18 system mRNA and protein expression was demonstrated in the eutopic endometrium of both adenomyosis and control women. Quantitative competitive PCR demonstrated that endometrial IL-18R mRNA and the ratio of IL-18BP to IL-18 were significantly increased in adenomyosis patients in comparison to the control group. Pearsons correlation showed a significant correlation between IL-18 and IL-18R in the eutopic endometrium of women with uterine adenomyosis, but not the control group. CONCLUSION(S) The expression of the eutopic endometrial IL-18 system and the ratio of antagonist to agonist at the level of the endometrial-myometrial interface (EMI) may possibly be responsible for the pathologic process of adenomyosis.

New perspectives on preimplantation genetic diagnosis and preimplantation genetic screening

Preimplantation genetic diagnosis is a procedure that involves the removal of one or more nuclei from oocytes (a polar body) or embryos (blastomeres or trophectoderm cells) in order to test for problems in genome sequence or chromosomes of the embryo prior to implantation. It provides new hope of having unaffected children, as well as avoiding the necessity of terminating an affected pregnancy for genetic parents who carry an affected gene or have balanced chromosomal status. Polymerase chain reaction-based molecular techniques are the methods used to detect gene defects with a known sequence and X-linked diseases. The indication for using this approach has expanded for couples who are prevented from having babies because they carry a serious genetic disorder to couples with conditions that are not immediately life threatening, such as cancer predisposition genes and Huntington disease. In addition, fluorescent in situ hybridization (FISH) has been widely applied for the detection of chromosome abnormalities. FISH allows the evaluation of many chromosomes at the same time, up to 15 chromosome pairs in a single cell. Preimplantation genetic screening, defined as a test that screens for aneuploidy, has been most commonly used in situations of advanced maternal age, a history of recurrent miscarriage, a history of repeated implantation failure, or a severe male factor. Unfortunately, randomized controlled trials have as yet shown no benefit with respect to preimplantation genetic screening using cleavage stage biopsy, which is probably attributable to the high levels of mosaicism at early cleavage stages and the limitations of FISH. Recently, two main types of array-based technology combined with whole genome amplification have been developed for use in preimplantation genetic diagnosis; these are comparative genomic hybridization and single nucleotide polymorphism-based arrays. Both allow the analysis of all chromosomes, and the latter also allows the haplotype of the sample to be determined. The promising results of these two approaches will inspire further validation of these array platforms, even at the single-cell level. It remains to be decided which embryo stage is the best for biopsy. Moreover, if randomized controlled trials are confirmed to play a role in increasing delivery rates, this will be a major step forward for assisted reproductive technology patients around the world.

Preimplantation genetic diagnosis by fluorescence in situ hybridization of reciprocal and Robertsonian translocations

OBJECTIVE The presence of reciprocal and Robertsonian chromosomal rearrangement is often related to recurrent miscarriage. Using preimplantation genetic diagnosis, the abortion rate can be decreased. Cases treated at our center were reviewed. MATERIALS AND METHODS A retrospective analysis for either Robertsonian or reciprocal translocations was performed on all completed cycles of preimplantation genetic diagnosis at our center since the first reported case in 2004 until the end of 2010. Day 3 embryo biopsies were carried out, and the biopsied cell was checked by fluorescent in situ hybridization using relevant informative probes. Embryos with a normal or balanced translocation karyotype were transferred on Day 4. RESULTS Thirty-eight preimplantation genetic diagnosis cycles involving 17 couples were completed. A total of 450 (82.6%) of the total oocytes were MII oocytes, and 158 (60.0%) of the two-pronuclei embryos were biopsied. In 41.4% of the fluorescent in situ hybridization analyses, the results were either normal or balanced. Embryos were transferred back after 21 cycles. Three babies were born from Robertsonian translocation carriers and another two from reciprocal translocation carriers. The miscarriage rate was 0%. Among the reciprocal translocation group, the live delivery rate was 8.3% per ovum pick-up cycle and 18.2% per embryo transfer cycle. Among the Robertsonian translocation group, the live delivery rate was 14.3% per ovum pick-up cycle and 20.0% per embryo transfer cycle. CONCLUSION There is a trend whereby the outcome for Robertsonian translocation group carriers is better than that for reciprocal translocation group carriers. Aneuploidy screening may possibly be added in order to improve the outcome, especially for individuals with an advanced maternal age. The emergence of an array-based technology should help improve this type of analysis.

Successful pregnancy in a woman with Kallmann's syndrome using human menopausal gonadotropin followed by low-dose human chorionic gonadotropin in the mid-to-late follicular phase.

Kallmann’s syndrome is characterized by hypogonadotropic hypogonadism and anosmia [1]. It is a rare disorder, occurring in only one per 50,000 women [2]. Induction of ovulation in women with hypogonadotropic hypogonadism requires follicle-stimulating hormone (FSH) for follicular growth, and both FSH and luteinizing hormone (LH) to induce optimal follicular steroidogenesis and ovulation. Numerous reports of achieving successful pregnancies in women with Kallmann’s syndrome have appeared in the literature. Recent evidence suggests that low-dose human chorionic gonadotropin (hCG) can also be used to mimic LH actions on developing follicles in a more sustained and stable manner, permitting the progression of folliculogenesis when the LH/ hCG receptors begin to be expressed in the granulose cells of larger ovarian follicles [3]. More specifically, serum levels of hCG during human menopausal gonadotropin (hMG) administration were inversely correlated with the occurrence of small preovulatory follicles [4]. We describe here a woman with Kallmann’s syndrome who was treated with a combination of hMG and low-dose hCG to achieve ovulation induction and successful pregnancy. A 29-year-old woman was referred to our hospital for investigation and treatment of infertility. She was first seen at the age of 19 years with a complaint of primary amenorrhea, having presented without any secondary characteristics and anosmia. She had very low serum gonadotropin and estrogen levels, and inadequate responses to repeated gonadotropinreleasing hormone (GnRH) tests. In addition, olfactory magnetic resonance imaging (MRI) revealed olfactory tract agenesis. She was diagnosed with Kallmann’s syndrome and

Low-dose GnRH antagonist protocol is as effective as the long GnRH agonist protocol in unselected patients undergoing in vitro fertilization and embryo transfer.

OBJECTIVE The present retrospective and controlled comparative study was designed to evaluate the pregnancy rate achieved using a modified, fixed, multiple-dose 0.125mg gonadotropin-releasing hormone (GnRH) antagonist protocol with the long GnRH agonist protocol as the control group. MATERIALS AND METHODS One hundred and twenty unselected women between 30 and 40 years of age, in their first cycle of IVF/ICSI, with a baseline follicle-stimulating hormone (FSH) <10 IU and an antral follicle count >3 were assigned into two groups: (1) the study group received 0.125mg of cetrorelix daily starting on Day 6 of stimulation; and (2) the control group received leuprolide daily starting in the mid-luteal phase of the preceding cycle. Both groups were given a flexible dose of recombinant FSH for stimulation. An ongoing pregnancy rate of more than 12 weeks was the primary outcome measure of the study. RESULTS Primary and secondary outcomes were comparable in both groups. A shorter duration of stimulation, a lower dosage of recombinant FSH consumption and a thinner endometrium on the day of human chorionic gonadotropin administration were all observed in the GnRH antagonist group. CONCLUSION A dosage of 0.125mg GnRH antagonist protocol was effective for these unselected patients during IVF/ET.

A gonadotropin releasing hormone agonist trigger of ovulation with aggressive luteal phase support for patients at risk of ovarian hyperstimulation syndrome undergoing controlled ovarian hyperstimulation

OBJECTIVE The aim of this study was to determine the efficacy and safety of luteal phase support using human chorionic gonadotropin (hCG) in cycles that are triggered with a gonadotropin-releasing hormone (GnRH) agonist in a moderate-to-high risk population undergoing a GnRH antagonist protocol. MATERIALS AND METHODS We retrospectively reviewed the charts of patients undergoing an in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle with a GnRH antagonist protocol from September 2011 to August 2012. The patients were defined as at high risk for ovarian hyperstimulation syndrome (OHSS) in terms of anti-Müllerian hormone (AMH) and antral follicle counts (AFCs). The patients were divided into two groups depending on whether ovulation was triggered with hCG or a GnRH agonist. Modified luteal support was provided for the cycles triggered by the GnRH agonist via low dose hCG (1500∼5000 IU). For the cycles that were triggered by hCG, urinary hCG (5000 IU) following two doses of recombinant hCG (250 μg) were administered. The primary outcomes of this study were the clinical pregnancy rate and the OHSS rate of the two groups. The secondary outcomes were the number of oocytes retrieved and the number of good quality embryos obtained. RESULTS The study group and the control group were similar in terms of the primary and secondary outcome measures. CONCLUSION Aggressive luteal support with low dose hCG following a GnRH agonist trigger can result in a comparable pregnancy rate to that with the use of a traditional hCG ovulation trigger. However, OHSS can still occur in patients with risk factors. Therefore, other OHSS prevention strategies should be considered.

Bilaterality of ovarian endometriomas does not affect the outcome of in vitro fertilization/intracytoplasmic sperm injection in infertile women after laparoscopic cystectomy

Background To assess whether the unilateral or bilateral lesions can affect ovarian reserve and pregnancy outcome in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in infertility patients underwent laparoscopic cystectomy. Methods A total of 148 IVF/ICSI cycle in patients who had undergone laparoscopic cystectomy for unilateral or bilateral endometriomas were reviewed retrospectively. There were 103 cycles where laparoscopic cystectomy had been carried out for unilateral endometriomas and 45 cycles after bilateral-side surgery. Primary outcome measures were ovarian reserve and ovarian response. Secondary outcome measures were the implantation rate, clinical pregnancy rate, and live birth rate. Results The number of dominant follicle on the day of human chorionic gonadotropin (hCG) administration (5.2 ± 3.1 vs. 4.2 ± 2.7; p = 0.048), and oocytes retrieved (10.0 ± 6.9 vs. 7.6 ± 6.6; p = 0.047) were significantly lower in the bilateral-side group compare with the unilateral-side group. However, the mean number of antral follicle count, metaphase II oocytes, the doses of gonadotropin used, fertilization rate, the rate of good quality embryos transferred, implantation rate and clinical pregnancy, live-birth rate and miscarriage rate were similar between the two groups. Conclusion There were no associations among the bilaterality of ovarian endometriomas, ovarian reserve and pregnancy outcomes in IVF/ICSI cycles. However, bilateral ovarian endometriomas after laparoscopic cystectomy may impair ovarian response as compared to unilateral ovarian endometrioma.

Conservative Laparoscopy Following Prophylactic Methotrexate for an Unruptured Bilateral Tubal Pregnancy

Bilateral simultaneous tubal pregnancy is a rare event. Conservative treatment is the standard method to preserve fertility. This report describes the use of a combination of laparoscopic salpingostomy and postoperative prophylactic methotrexate (MTX) in a woman with bilateral tubal pregnancy in order to preserve fertility successfully. A 25-year-old woman, gravida 1, para 0, abortus 1, suffered from secondary amenorrhea combined with intermittent vaginal bleeding and dull lower abdominal pain 1 week before she was referred to our medical center. Her gynecologic history showed secondary infertility of more than 1 year. There was no history of pelvic inflammatory disease, intrauterine contraceptive device use, or major pelvic surgery. Urinary pregnancy test was positive after the second course of clomiphene citrate (Clomid; YunHsin, Taichung, Taiwan), with 100 mg administered orally, from days 5–9 of the menstrual cycle at a private clinic. However, no intrauterine pregnancy was revealed on serial ultrasonography. Serum human chorionic gonadotropin (hCG) level showed an abnormal rise (11,000 IU/L initially vs. 17,000 IU/L 4 days after initial measurement). She was then transferred to our tertiary center. Vaginal ultrasound scan was performed, confirming the absence of a gestational sac in the uterus and showing the presence of abdominal fluid and a right adnexal mass measuring 3.2 × 2.8 cm. Laparoscopic surgery was arranged under the impression of extrauterine pregnancy. In the operating room, about 200 mL of blood was found in the cul-de-sac. Both tubes had an ampullary pregnancy (Figure).