Toshihiro Fujiwara

Decreased pregnancy rate is linked to abnormal uterine peristalsis caused by intramural fibroids

BACKGROUND The relationship between fibroids and infertility remains an unsolved question, and management of intramural fibroids is controversial. During the implantation phase, uterine peristalsis is dramatically reduced, which is thought to facilitate embryo implantation. Our aims were to evaluate (i) the occurrence and frequency of uterine peristalsis in infertile women with intramural fibroids and (ii) whether the presence of uterine peristalsis decreases the pregnancy rate. METHODS Ninety-five infertile patients with uterine fibroids were examined using magnetic resonance imaging (MRI). Inclusion criteria were as follows: (i) presence of intramural fibroids, excluding submucosal type; (ii) no other significant infertility factors (excluding endometriosis); and (iii) regular menstrual cycles, and MRI performed at the time of implantation (luteal phase day 5-9). The frequency of junctional zone movement was evaluated using cine-mode-display MRI. After MRI, patients underwent infertility treatment for up to 4 months, and the pregnancy rate was evaluated prospectively. RESULTS Fifty-one patients fulfilled the inclusion criteria, and 29 (57%) and 22 (43%) patients were assigned to the low (0 or 1 time/3 min) or high frequency (≥ 2 times/3 min) uterine peristalsis group, respectively. Endometriosis incidence was the same in both groups. Ten out of the 29 patients (34%) in the low-frequency group achieved pregnancy, compared with none of the 22 patients (0%) in the high-frequency group (P< 0.005). Comparing pregnant and non-pregnant cases, 4 of 10 patients (40%) and 9 of 41 patients (22%), respectively, had endometriosis (not significant). CONCLUSIONS A higher frequency of uterine peristalsis during the mid-luteal phase might be one of the causes of infertility associated with intramural-type fibroids.

Stem cell factor (SCF) concentrations in peritoneal fluid of women with or without endometriosis.

PROBLEM: In the quest for possible involvement of stem cell factor (SCF), a cytokine known to have multiple effects, in the pathogenesis of endometriosis, we evaluated concentrations of SCF in peritoneal fluid (PF) of women with or without endometriosis.
 METHOD OF STUDY: SCF concentrations in PF collected from women undergoing laparoscopy were measured, using a specific enzyme‐linked immunosorbent assay (ELISA). Reverse transcription‐polymerase chain reaction (RT‐PCR) analysis to detect gene expression of c‐kit, the receptor for SCF, was performed using the endometriotic tissue and the eutopic endometrium collected during the operation.
 RESULTS: SCF concentrations in PF of women with endometriosis were significantly higher compared to women without endometriosis. Looking at SCF concentrations in PF of women with endometriosis stratified by disease stage, women with stage I and II exhibited relatively higher SCF levels in PF, whereas SCF levels in PF with stage III and IV were comparable with those without endometriosis. The expression of mRNA for c‐kit was detected in both the endometriotic tissue and the eutopic endometrium.
 CONCLUSION: We demonstrated an elevation in SCF levels in PF associated with endometriosis and the presence of its receptor in endometriotic tissues. Given the known pleiotropic properties of SCF, the present results suggest that SCF might play a role in the pathogenesis of endometriosis.

Concentrations of interferon-gamma-induced protein-10 (IP-10), an antiangiogenic substance, are decreased in peritoneal fluid of women with advanced endometriosis.

Problem:  To assess whether interferon‐γ‐induced protein‐10 (IP‐10), a chemokine that has antiangiogenic activities, may be involved in the pathogenesis of endometriosis.

Human Chorionic Gonadotropin Combined with Progesterone for Luteal Support Improves Pregnancy Rate in Patients with Low Late-Midluteal Estradiol Levels in IVF Cycles

AbstractPurpose: To investigate how late-midluteal estradiol levels relate to the pregnancy outcome in IVF cycles, and to assess whether human chorionic gonadotropin (hCG) for luteal support benefits the pregnancy outcome of patients with low late-midluteal estradiol levels. Methods: The pregnancy rate of 436 women undergoing first IVF cycles with long protocol and luteal support with progesterone alone were analyzed. Unsuccessful women with low late-midluteal estradiol levels (<100 pg/mL) proceeded with the exploratory second IVF cycles where they were randomly given with either progesterone alone (P protocol) or hCG +progesterone (P+hCG protocol) for luteal support. Results: Pregnancy rate in women with low late-midluteal estradiol levels was significantly lower compared to that with medium (100–500 pg/mL) and high (>500 pg/mL) levels (13.3, 26.8, and 36.3%, respectively). P+hCG protocol increased late-midluteal estradiol levels and produced a significantly higher pregnancy rate (31.7%) than P protocol (13.7%). Conclusions: hCG in combination with progesterone for luteal support was suggested to benefit women undergoing IVF with low late-midluteal estradiol levels.

Myomectomy Decreases Abnormal Uterine Peristalsis and Increases Pregnancy Rate

BACKGROUND The relationship between fibroids and infertility remains a critical and unresolved question. During the implantation phase, it is known that uterine peristalsis is dramatically reduced, which is thought to facilitate implantation of the embryo to the endometrium. In the previous study, using a cine MRI mode, we found that less than half of the patients with intramural fibroids exhibited abnormal uterine peristalsis during the mid-luteal phase. In the present study, we further investigated whether myomectomy for patients in the high peristalsis group is a constructive method to normalize uterine peristalsis. METHODS The frequency of junctional zone movement was evaluated using a cine MRI mode during the mid-luteal phase. Fifteen infertility patients, who had intramural myomas and exhibited abnormal uterine peristalsis (≥2 times/3 min) in their first MRI, underwent myomectomy and a second MRI. After receiving the second MRI, patients underwent infertility treatment for at least 8 months, and pregnancy rate was evaluated prospectively. RESULTS Among 15 patients, the frequency of uterine peristalsis was normalized (0 or 1 time/3 min) in 14 patients. Following myomectomy and second MRI test, 6 of the 15 patients achieved pregnancy (n = 15, pregnancy rate: 40%). CONCLUSIONS The presence of uterine fibroids might induce abnormal uterine peristalsis in some patients, leading to infertility, and myomectomy may improve fertility in these patients.

Analysis of follicular fluid hormone concentrations and granulosa cell mRNA levels for the inhibin-activin-follistatin system: relation to oocyte and embryo characteristics

OBJECTIVE To explore the potential roles of inhibin, activin, and follistatin in human oocyte development by quantifying their intrafollicular biosynthesis. DESIGN Prospective, nonrandomized study. SETTING An IVF unit and academic research laboratory. PATIENT(S) Thirty one patients undergoing IVF. INTERVENTION(S) Human menopausal gonadotropins or human FSH (or both) were administered. Single-follicle aspirates (n = 110) were collected for analysis. MAIN OUTCOME MEASURE(S) Concentrations of dimeric, total and pro-alphaC inhibin forms; activin A; follistatin; estradiol; and progesterone were measured in follicular fluids. Granulosa-cell mRNA was analyzed for alpha, beta A, and beta B inhibin and activin subunits; follistatin; activin receptors; and beta-actin. Hormone concentrations and mRNA levels were correlated with oocytes or embryos from the same follicles. RESULT(S) Levels of progesterone and follistatin were significantly greater in follicles containing MI or MII oocytes than in those containing GV oocytes. Inhibin alpha-subunit mRNA levels were significantly higher in follicles containing maturing oocytes, the highest-quality oocytes, and oocytes that were subsequently fertilized. In contrast, inhibin alpha-subunit mRNA levels were significantly lower in follicles from which higher-quality embryos were obtained. CONCLUSION(S) Inhibin alpha-subunit biosynthesis is associated with normal oocyte and follicle maturation, but excessive alpha-inhibin is associated with poor embryo quality. None of the hormones analyzed were associated with oocyte or embryo quality.

Upregulation of Interleukin-8 by Hypoxia in Human Ovaries

Problem: To evaluate the effect of hypoxia on interleukin (IL)‐8 expression in human ovarian follicles.

Conjoined twins in a triplet pregnancy after intracytoplasmic sperm injection and blastocyst transfer: case report and review of the literature

OBJECTIVE To describe an exceptional case of conjoined twins in a triplet pregnancy after intracytoplasmic sperm injection (ICSI) and blastocyst transfer. DESIGN Case report. SETTING University teaching hospital reproductive endocrinology department and infertility practice. PATIENT(S) A 34-year-old woman underwent ICSI and received two blastocysts transferred. INTERVENTION(S) Transvaginal ultrasonography performed sequentially during early pregnancy. MAIN OUTCOME MEASURE(S) Ultrasound images of the fetus in gestational sac. RESULT(S) Two gestational sacs in the uterus were revealed at the 5th week. At the 8th week of gestation, a single fetus was seen in one sac, whereas thoracopagus conjoined twins was diagnosed in the other sac. At the 10th week, the conjoined twins had a spontaneous cardiac arrest confirmed by color Doppler. The subsequent course was uneventful, and a healthy child was born at 39th week. CONCLUSION(S) To date, a small number of cases of conjoined twins in IVF/ICSI pregnancies have been reported, in which most cases were treated with manipulations causing possible trauma in the zona pellucida. Our case is unique in that the transferred embryos were blastocysts that might have had additional damage on the zona pellucida from the longer culture.

Usefulness of Long-Jaw Forceps in Laparoscopic Cornual Resection of Interstitial Pregnancies

Although laparoscopic surgery could be an option for treating interstitial pregnancies, it has not gained wide acceptance largely because of difficulty achieving hemostasis. To overcome this, we employed long-jaw forceps in three cases of interstitial pregnancy that were successfully treated by laparoscopic cornual resection. The forceps grasped a relatively large portion of pregnant myometrium without slipping, thus securing hemostasis and facilitating suturing.

Case of chronic ectopic pregnancy diagnosed in which the complete shape of the fetus was visible by ultrasonography

Preoperative diagnosis of chronic ectopic pregnancy is often difficult because of the high incidence of negative results on pregnancy tests as a consequence of the very small amount of live villi, subtle symptoms, and the poor specificity of ultrasonographic patterns. A 45‐year‐old woman was referred to our department for evaluation of a mass 8 cm in diameter with solid parts in the right adnexal area. Transvaginal ultrasonography showed a mass consisting of a cystic part with an irregular thick capsule distinct from the right ovary. In the center of the cystic part, a fetus‐like image, 20 mm in length was seen. Preoperative diagnosis was confirmed by the laparoscopy, which revealed a swollen right tube containing a fetus with highly necrotic changes. This case was unique because chronic ectopic pregnancy was detected at an early stage before absorption of the conceptus occurred, which coincidentally is an appropriate time for morphological diagnosis.