Ineffectiveness of antenatal guidance intervention for vitamin D insufficiency and deficiency in pregnant women in Kyoto, Japan.

AIM: The aim of this study was to investigate the vitamin D status among healthy pregnant women in Japan, and to evaluate the effectiveness of the antenatal health guidance intervention for the pregnant women who were informed about their low vitamin D levels. METHODS: We measured the level of 25-hydroxyvitamin D (25[OH]D) using chemiluminescent immunoassay among the singleton pregnant women who received at antenatal routine check-up (8-24 weeks of gestation) with written consent during September 2017-September 2018. The measurement values were informed by the concerned physician and health guidance intervention was given to the pregnant women with inadequate Vitamin D status (25[OH]D < 30 ng/mL). At around 36 weeks of gestation, the measurement of 25(OH)D and a questionnaire regarding behavioral changes after the guidance was conducted. RESULTS: The average value of 25(OH)D of 1192 pregnant women before the guidance was 14.89 ± 4.85 ng/mL, and the prevalence of sufficient vitamin D status (25(OH)D ≥ 30 ng/mL) was 0.67% (8/1192). Nine hundred eighty-two pregnant women who had inadequate vitamin D status were followed, thereafter-guidance prevalence of sufficiency was 1.02% (10/982); insufficiency, 14.66% (144/982); and deficiency, 84.32% (828/982), respectively. Although the prevalence of deficiency was decreased after guidance intervention significantly, the prevalence was still high and the effect on behavioral changes was a little. CONCLUSION: The prevalence of vitamin D sufficient status among pregnant women in Japan was extremely low, which is a serious condition. It was also revealed the effectiveness of the antenatal health guidance intervention for pregnant women was not enough.

Barriers for sperm cryopreservation in advanced germ cell tumor patients: a 20-year experience.

BACKGROUND: This study aimed to investigate barriers to sperm cryopreservation for patients with advanced germ cell tumors. METHODS: We reviewed data collected from patients who underwent chemotherapy for advanced germ cell tumors in our institutions from 1996 to 2016. We divided sperm cryopreservation procedures into three steps: offering information about sperm cryopreservation, patients' decision making and sperm collection, and investigating the barriers in each step. RESULTS: Of the 91 patients, 43 (47%) successfully completed sperm cryopreservation. Thirty (33%) patients were not offered information about sperm cryopreservation from the doctors. Nine patients (9.9%) were offered but declined preservation. Nine patients (9.9%) were not able to provide sperm because of azoospermia (5) and anejaculation (4). Among 43 patients who successfully provided sperm, 10 (23%) had their cryopreserved sperm used for 21 cycles of in vitro fertilization. Ten pregnancies and 7 fatherhoods were achieved. Thirteen patients (30%) had their cryopreserved sperm discarded without use, whereas 20 (47%) continued preserving their sperm for a median 12.5 years. CONCLUSIONS: Not only offering proper information about sperm cryopreservation, but also shared decision making prior to chemotherapy, and considering fertility preservation before orchiectomy are imperative. The rate of use of preserved sperm was relatively high, but decision making for sperm disposal should also be supported.

Sperm cryopreservation: Clinical and fertility outcomes in male oncological patients with germ cell tumors or hematological disorders.

PURPOSE: There is insufficient understanding of the effects of malignant diseases themselves and chemotherapy on semen quality and final fertility outcomes. Here, the authors focused on the patients with malignant diseases who cryopreserved sperm pre- or post-chemotherapy for future fertility, and revealed how clinical settings can affect semen quality and final outcomes. METHODS: The authors reviewed the records of 257 patients with malignant diseases who cryopreserved sperm. Among 257 cases, 113 men with germ cell tumors (GCTs) and 111 men with hematological disorders (HDs) were included in this study. Twenty-five patients who achieved successful outcomes using cryopreserved sperm were also analyzed. RESULTS: In the men with GCTs and HDs, respectively, differences were observed in age (28 vs 27 years), sperm concentration (32.6 vs 46.1 million/mL, P < 0.05), motility (42.2% vs 41.0%), and the rate of cryopreservation before chemotherapy (90% vs 59%, P < 0.0001). For successful pregnancies and deliveries, age at cryopreservation (30.0 vs 35.3 years, P < 0.05) and disease type (12/16 vs 3/9, P < 0.05) were significant factors. CONCLUSIONS: Compared to patients with GCTs, those with HDs have a lower pregnancy and delivery rate, even though semen quality is higher. Disease type and age at cryopreservation are significant factors for successful outcomes.

Sphingolipid pathway regulates innate immune responses at the fetomaternal interface during pregnancy.

For a successful pregnancy, the mother's immune system has to tolerate the semiallogeneic fetus. A deleterious immune attack is avoided by orchestration of cellular, hormonal, and enzymatic factors. However, the precise mechanisms underlying fetomaternal tolerance are not yet completely understood. In this study, we demonstrate that sphingolipid metabolism constitutes a novel signaling pathway that is indispensable for fetomaternal tolerance by regulating innate immune responses at the fetomaternal interface. Perturbation of the sphingolipid pathway by disruption of the sphingosine kinase gene (Sphk) during pregnancy caused unusually high expression of neutrophil chemoattractants, CXCL1 and CXCL2, in the decidua, leading to a massive infiltration of neutrophils into the fetomaternal interface with enhanced oxidative damage, resulting in early fetal death. Sphk-deficient mice also exhibited neutrophilia in the peripheral blood, enhanced generation of granulocytes in the bone marrow, and a decrease in the number of decidual natural killer cells. The blockage of neutrophil influx protected Sphk-deficient mice against pregnancy loss. Notably, a similar result was obtained in human decidual cells, in which Sphk deficiency dramatically increased the secretion of CXCL1 and IL-8. In conclusion, our findings suggest that the sphingolipid metabolic pathway plays a critical role in fetomaternal tolerance by regulating innate immunity at the fetomaternal interface both in mice and humans, and it could provide novel insight into the development of therapeutic strategies to treat idiopathic pregnancy loss in humans.

Uterine peristalsis in women with repeated IVF failures: possible therapeutic effect of hyoscine bromide.

BACKGROUND: Uterine peristalsis, which is influenced by hormonal and cholinergic effects, may have a role in successful implantation and continuing pregnancy. CASES: We encountered abnormal uterine peristalsis in three women who had had repeated in vitro fertilization (IVF) treatment failures. They subsequently had successful pregnancies when hyoscine bromide was administered at the time of embryo transfer. CONCLUSION: It is possible that decreasing uterine peristalsis with use of an anticholinergic agent during IVF treatment facilitates retention of embryos and increases the probability of successful pregnancy.

[Sperm cryopreservation for cancer patients: 5-year experience in a private hospital in Japan].

Private hospitals in Japan appear to play an important role in the fertility preservation in cancer patients. However, only a few university-related institutions have published their data about sperm banking. Here we report our experience in a private hospital. The database of 5 years of experience with sperm cryopreservation for male cancer patients was reviewed. We assessed the type of cancer, timing of collection, sperm quality, and utilization for reproductive purposes. There were a total of 88 oncology patients who underwent sperm banking at our institution during the study period. Types of cancer were various, with testicular cancer and hematological malignancies comprising the largest groups. Nearly 90% of the testicular cancer patients had their sperm preserved prior to the therapy, while only 53% of those with hematological disease did so. Evaluation of semen parameters for these groups revealed that oligozoospermia in testicular cancer patients, even prior to initiation of cancer therapy, was common. Five patients utilized their specimens for reproductive purposes. Of these, 3 patients successfully fathered a child. Our results suggest that sperm cryopreservation before initiation of cancer therapy in male oncology patients is under-utilized. Additionally, there is minimal use of cryopreserved specimens for reproductive purposes. This under-utilization is supposed to be due to physicians', especially hematologists', insufficient awareness toward chemotherapy-related infertility and the paucity of reports regarding reproductive outcome after freezing. More data should be compiled to help both physicians and patients who are considering sperm cryopreservation.

[Testicular Leydig cell tumor presenting as male infertility: a case report].

A Leydig cell tumor is a rare disease entity occurring in the testis. Occasionally it is considered to be related to male infertility. We report a case study of a Leydig cell tumor in a single testis presenting as male infertility. A 38-year-old male was referred to our hospital because of a tumor in his right testis. He had undergone left orchiectomy at one year old because of a testicular tumor. During an examination related to the infertility, ultrasound revealed a 1 cm tumor. Tumor markers were all within normal ranges.Hormonal examination showed that luteinizing hormone (LH) 30.3 mIU/ml (1.5-12.4) and follicle stimulating hormone (FSH) 11.9 mIU/ml (1.7-8.6) were higher than normal limits, but total testosterone(total T) and estradiol (E2) were within normal ranges. Tumor enucleation was first performed, and then testicular sperm extraction (TESE) was carried out from a macroscopically normal site of the testis.Histopathological diagnosis was a benign Leydig cell tumor surrounded by Leydig cell hyperplasia. For 12 months after the operation there has been no recurrence. Although high LH and FSH persisted, total T and E2 were within normal ranges.

Craniotabes in normal newborns: the earliest sign of subclinical vitamin D deficiency.

CONTEXT: Craniotabes in otherwise normal neonates has been regarded as physiological and left untreated. OBJECTIVE: Our objective was to investigate the role of vitamin D deficiency in the development of craniotabes in normal neonates. DESIGN AND SETTING: Newborn screening of craniotabes was conducted at the single largest obstetrical facility in Kyoto, Japan. Follow-up study at 1 month was conducted at Kyoto University Hospital. SUBJECTS: A total of 1120 consecutive normal Japanese neonates born in May, 2006, through April, 2007, were included in the study. MAIN OUTCOME MEASURES: The incidence of craniotabes was scored each month. Neonates with craniotabes were followed up at 1 month with measurements of serum calcium, phosphorus, alkaline phosphatase (ALP), intact PTH, 25-OH vitamin D (25-OHD), urinary calcium, phosphorus, creatinine, and hand x-rays. RESULTS: Craniotabes was present in 246 (22.0%) neonates, and the incidence had obvious seasonal variations, highest in April-May and lowest in November. At 1 month, infants with craniotabes had significantly higher serum ALP compared with normal neonates; 6.9% of them had elevated intact PTH over 60 pg/ml, and 37.3% had 25-OHD less than 10 ng/ml. When separately analyzed according to the method of feeding, 56.9% of breast-fed infants showed 25-OHD less than 10 ng/ml, whereas none of formula/mixed-fed infants did, and breast-fed infants had significantly higher serum PTH and ALP compared with formula/mixed-fed infants. SUMMARY: These results suggest that craniotabes in normal neonates is associated with vitamin D deficiency in utero, and the deficiency persists at 1 month in many of them, especially when breast-fed.

[The Aging Male's Symptoms (AMS) scale in Japanese men attending an infertility clinic].

There is a gradual decline in testosterone and free testosterone with age. Physical and psychological changes can occur due to this decline of androgens--a syndrome known as "partial androgen decline in the aging male" (PADAM). Male infertility and erectile dysfunction (ED) can also be caused by androgen deficiency. Thus, male infertility, ED and PADAM are interrelated. We evaluated the prevalence of PADAM symptoms in 215 infertile patients in an infertility clinic using the Aging Males Symptom (AMS) scale. Results of the evaluation of 301 men, (30-39 years old) using the same scale, who were part of a multiphasic health screening program, served as controls. The total score of the infertile patients was lower than that of the controls. Especially, the scores of the psychological and somatic subscales were significantly lower in infertile patients (P=0.009, P=0.012, respectively). Thirty three (15.3%) of the 215 infertile patients had ED. Although the score of sexual subscale was higher in the ED patients than in the controls, the scores of the psychological and somatic subscales were not significantly different from those in the controls. In conclusion, PADAM symptoms in Japanese infertile patients were not severe. Moreover, general function was better preserved in the infertile patients than in the controls. The psychological and somatic functions of ED patients were also well preserved.