Outcomes of Ovulation Induction Aimed to Pregnancy in Eight Hypopituitarism Patients.

BACKGROUND: Female sex hormones work in concert. Gonadotropin-releasing hormone and ovulation-inducing agents are required in female patients with infertility owing to hormone dysregulation. Although drug-induced follicular development can be expected in patients with endogenous female hormone deficiency, data are lacking on the protocols and drugs used. METHODS: We retrospectively examined the success rates of ovulation induction, assisted reproductive technology, and pregnancy outcomes in 66 cycles of eight patients with pituitary insufficiency at our hospital. RESULTS: Ovulation occurred in 75.4% (49/66); 82.6% (38/46) of patients <40 years and 57.9% (11/19) of patients ≥40 years of age. Five of the eight patients became pregnant, and three delivered babies. The fertilization rate was 78% with in vitro fertilization, and the recombinant follicle-stimulating hormone usage was 3,717.1 ± 1,528.9 International Unit in hypopituitarism patients. CONCLUSION: Hypopituitarism patients can achieve ovulation, pregnancy, and delivery after optimal gonadotropin administration. Further studies are needed to determine the effects of gonadotropins on other pituitary hormones, such as growth hormones.

COVID-19 infection control protocol and acceptance in an ART in vitro fertilization hospital.

Purpose: In Tokyo, where the highest coronavirus disease 2019 (COVID-19) infection rates have been reported nationally, we introduced and performed polymerase chain reaction (PCR) testing on the patients prior to them coming for oocyte retrieval (OR) or embryo transfer (ET) procedures. In addition, we recommended that patients self-inject ovarian stimulation drugs to reduce the number of hospital visits required. We aimed to assess the patient acceptance of these measures and the change of treatment number. Methods: We conducted a retrospective study examining the patients coming for OR or ET, from the first time a state of emergency was declared in Japan, May 2020, until September 2021. Results: A total of 79 out of 94 (94%) patients complied with the measures. This may reflect that PCR universal screening was accepted by most patients as necessary for reducing infection spread. In addition, the number of patients receiving OR and ET increased. The widespread adoption of work-from-home practices during the pandemic has made outpatient visits more acceptable to the general public. Conclusions: Universal screening and self-injection are accepted and effective infection measures in patients presenting for OR and ET.

A Case of Unsuspected Low-grade Endometrial Stromal Sarcoma Successfully Treated with Two Minimally Invasive Surgeries.

It is relatively uncommon to treat patients with a preoperative diagnosis of benign leiomyoma that is then unexpectedly rediagnosed as malignant in postoperative histology. We report the case of a 55-year-old woman with low-grade endometrial stromal sarcoma who had been diagnosed as having uterine leiomyoma with myxoid degeneration by preoperative magnetic resonance imaging (MRI). She underwent a laparoscopic hysterectomy. The uterus, after being placed in a retrieval bag, was transvaginally morcellated to prevent spillage of the contents, as the MRI image appeared somewhat atypical. A retrospective survey of MRI findings affirmed that the muscle tissue had the appearance of a low-intensity band-like structure: bag of worms appearance. She underwent a laparoscopic bilateral salpingo-oophorectomy and remains recurrence-free. With somewhat atypical preoperative MRI, it is essential to prevent the spillage of the tumor content as no definitive preoperative exclusion of unsuspected mesenchymal malignancies is feasible.

A case of ovarian teratoma with nephroblastoma presenting spontaneous rupture.

Nephroblastoma (also known as Wilms' tumor) mainly occurs in the kidneys of children. Nephroblastoma outside the kidneys may be observed in three situations: primary disease, metastatic disease and nephroblastoma arising in teratoma. Teratoma with nephroblastoma (TWN) of the adult ovary is a rare tumor and only one case has been reported. We report an unusual adult case of ovarian TWN presented to us with acute abdomen due to the spontaneous rupture of the ovary. The rupture occurred at the site of TWN, while contralateral ovary with only mature cystic teratoma component had no rupture. After one and a half months of the ovary sparing surgery, the tumor disseminated to the splenic hilum and the omentum. A complete staging with maximum cytoreduction followed by adjuvant chemotherapy were performed. She remains disease free until present.

A case of rapidly-growing atypical polypoid adenomyoma which was histologically diagnosed before operation and removed by a laparoscopic resection.

OBJECTIVE: Atypical polypoid adenomyoma (APAM) is an epithelial-mesenchymal mixed tumor which often develops in the uterine cavity of reproductive age women, requiring preservation of the reproductive functions. Preoperative endometrial biopsy may not yield histological diagnosis as the tumor is a solid smooth muscle tumor. The standard treatment option is a hysteroscopic resection for the diagnosis and the treatment at the same time. CASE REPORT: We report a case of rapidly-growing APAM successfully diagnosed preoperatively via transcervical punch biopsy followed by a laparoscopic resection. The mass was relatively large, had been located in the lower segment of the uterus, and the area of contact with the muscular layers was large. It was a complete removal and no recurrence had been observed 9 months after the operation. CONCLUSION: This is the first report of APAM treated by laparoscopic resection. The method may be a useful alternative when hysteroscopic surgery is inappropriate.

Current status of preimplantation genetic diagnosis in Japan.

This is a retrospective study aimingto clarify the current status of preimplantation genetic diagnosis (PGD) in Japan. Our data were collected from 12 facilities between September 2004 and September 2012, and entered into a database. A majority of PGD in Japan was performed for balanced structural chromosomal abnormalities in couples with recurrent miscarriage. PGD for monogenic diseases was performed only in two facilities. The average maternal age was 38 years for monogenic diseases and 40 years for chromosomal abnormalities. Overall there have been671 cycles to oocyte retrieval reported. Of these cycles, 85% (572 cycles)were for chromosomal abnormalities, and 15% (99 cycles) for monogenic diseases. Diagnosis rates in the current study were 70.8% for monogenic diseases and 94.0% for chromosomal abnormalities. Rates of embryo transfer of PGD were 62.7% for monogenic diseases and 25.5% for chromosomal abnormalities. Clinical pregnancy rates per embryo transfer were 12.0% for monogenic diseases and 35.6% for chromosomal abnormalities. Our study is the first PGD report from all facilities which had the approval of the ethics committee of the Japanese Society of Obstetrics and Gynecology. We have built a basis for gathering continuous PGD data in Japan.

C-kit expression in spermatogonia damaged by doxorubicin exposure in mice.

AIM: The purpose of this study was to assess the relationship between chronically impaired spermatogenesis induced by exposing mice to doxorubicin (DXR) and expression of the infertility factor c-kit. METHOD: Eight-week-old male Institute for Cancer Research (ICR) mice were intraperitoneally treated with DXR (0.15 mg/kg, DXR group) or saline (0.15 mg/kg, control group) twice weekly for five weeks and were killed 14 weeks after initial exposure. The animals were sacrificed and bilateral testes were removed and weighed. The testes were stored for the mRNA assay and were fixed for immunohistochemistry. Some testicular samples were fixed in 10% formalin for histopathological examination. RESULTS: Testicular weight (67.6 ± 9.7 mg, P < 0.05), sperm motility (18 ± 6.0%, P < 0.05) and the fertilization rate (2-to-16-cell embryos, 5%; P < 0.05) were significantly lower in the DXR group than in the control group. In the DXR group there was severe tissue damage from the spermatogonia onward, and the Sertoli cell ratio was lower in the DXR group than in the control group (38% vs. 9%, P < 0.05). In addition, there was a decrease in c-kit protein expression, and the amount of c-kit messenger ribonucleic acid (mRNA) expression according to a semiquantitative method was also decreased. CONCLUSION: Expression of c-kit in the mice with chronically impaired spermatogenesis induced by long-term, low-dose administration of DXR correlated with the decrease in the number of spermatogonia.

Green tea extracts attenuate doxorubicin-induced spermatogenic disorders in conjunction with higher telomerase activity in mice.

PURPOSE: The aim of this study was to investigate the protective effect of green tea extracts against doxorubicin-induced damage in the mouse testes correlating with telomerase activity. METHODS: Green tea extracts were administered orally. Doxorubicin was coadministered intraperitoneally. These testes were evaluated histologically and the telomerase activity was analyzed. Additional immunostaining was carried out. RESULTS: Both the sperm density and sperm motility were significantly increased in green tea extracts coadministration groups as compared to the doxorubicin-treated groups. By histological analysis, germ cell damage was greatly attenuated by green tea extracts coadministration. Telomerase activity significantly increased in association with the coadministration of green tea extracts as compared to that of doxorubicin-only groups. In all groups, human telomerase reverse transcriptase signals were mainly observed in the spermatocytes and spermatids. CONCLUSIONS: These findings suggest that green tea extracts exert protective effects against doxorubicin-induced spermatogenic disorders in conjunction with higher telomerase activity levels.

The development of novel quantification assay for mitochondrial DNA heteroplasmy aimed at preimplantation genetic diagnosis of Leigh encephalopathy.

PURPOSE: To perform preimplantation genetic diagnosis (PGD) of Leigh encephalopathy, we developed a rapid and reliable quantification assay for the percentage of T8993G mtDNA mutation and analyzed various specimens. METHODS: We prepared the standard curve by measuring serial proportion of 8993T/G cloned plasmid DNA using real-time PCR, and measured (1) mutant DNA (known proportions by PCR-RFLP), (2) single lymphocytes from 46% mutant carrier, (3) 123 blastomeres from 20 abnormal embryos. RESULTS: (1) These were within -5 - +6% error range, (2) mean 44.3%(11-70%), (3) Five embryos harbored T8993G mutation (4-22%). Embryos from same person indicated different degrees of heteroplasmy, and blastomeres from same embryo demonstrated limited dispersion of heteroplasmy (2-11%). CONCLUSIONS: (1) This method provides rapid and reliable PGD for Leigh encephalopathy. (2) The variable heteroplasmy with somatic mitosis was suggested. (3) T8993G mutation was existed in undeveloped embryo, and the bottleneck theory was supported. The limited heteroplasmy dispersion of blastomeres from same embryo also supported reliability of PGD for T8993G mutation.

Well-devised quantification analysis for duplication mutation of Duchenne muscular dystrophy aimed at preimplantation genetic diagnosis.

PURPOSE: Preimplantation genetic diagnosis (PGD) has been performed for deletion and point mutation type of Duchenne muscular dystrophy (DMD). Our aim was to develop a PGD technique, not yet established, to directly detect duplication mutation instead of substitute diagnosis similar to gender determination. METHODS: Our method is based on comparative quantification using conventional duplex PCR, real-time PCR and gender determination. We evaluated this method in single lymphocytes from a duplication type of DMD patient and a normal male. RESULTS: There was a significant difference in the mean values of the ratios (the mutation locus/a normal reference): mean value +/- SE was 1.84 +/- 0.15 in the duplication patient, and 1.00 +/- 0.09 in the normal male (p < 0.001). CONCLUSION: It is suggested that our comparative quantification method could be a new option in PGD for carriers with duplication mutation who wish to have an unaffected son.

Synthesis of crystallized mesoporous transition metal oxides by silicone treatment of the oxide precursor.

Ordered mesoporous transition metal oxides were successfully crystallized after strengthening the amorphous framework by a silica layer, which efficiently protected the original mesoporous structure against crystallization and resulting mass transfer.

Association of male infertility with Pro185Ala polymorphism in the aryl hydrocarbon receptor repressor gene: implication for the susceptibility to dioxins.

OBJECTIVE: To examine whether Arg554Lys polymorphism in the gene for aryl hydrocarbon receptor (AHR) and/or Pro185Ala polymorphism in the gene for aryl hydrocarbon receptor repressor (AHRR) constitutes a susceptibility locus for dioxin-related male infertility. DESIGN: Association study of male infertility with polymorphisms. SETTING: National research institute and university hospitals. PATIENT(S): 123 Japanese men with azoospermia or severe oligozoospermia and 112 men with proven fertility. INTERVENTION(S): Polymorphism analysis. MAIN OUTCOME MEASURE(S): The allele and genotype frequencies between infertile men and controls. RESULT(S): The allele and genotype frequencies of the AHR polymorphism were comparable between infertile men and controls. By contrast, although the difference in the allele frequency of the AHRR polymorphism did not reach a significant level, the genotype frequency was statistically significantly different between the two groups of men. Furthermore, the statistical difference became more significant when the frequency was compared between the Pro/Pro genotype and the Pro/Ala plus Ala/Ala genotype. CONCLUSION(S): The Pro185Ala polymorphism in AHRR may constitute a susceptibility locus for dioxin-related male infertility. It appears that the negative feedback effect of AHRR on dioxin-related signaling is weaker for the proline allele than for the alanine allele, and that the hypomorphic function of the proline allele exerts a recessive adverse effect on male fertility.