Urethral injection of dedifferentiated fat cells ameliorates sphincter damage and voiding dysfunction in a rat model of persistence stress urinary incontinence.

PURPOSE: Dedifferentiated fat (DFAT) cells are mature adipocyte-derived multipotent cells that can be applicable to cell-based therapy for stress urinary incontinence (SUI). This study developed a persistence SUI model that allows long-term evaluation using a combination of vaginal distention (VD) and bilateral ovariectomy (OVX) in rats. Then, the therapeutic effects of DFAT cell transplantation in the persistence SUI model was examined. METHODS: In total, 48 Sprague-Dawley rats were divided into four groups and underwent VD (VD group), bilateral OVX (OVX group), VD and bilateral OVX (VD + OVX group), or sham operation (Control group). At 2, 4, and 6 weeks after injury, leak point pressure (LPP) and histological changes of the urethral sphincter were evaluated. Next, 14 rats undergoing VD and bilateral OVX were divided into two groups and administered urethral injection of DFAT cells (DFAT group) or fibroblasts (Fibroblast group). At 6 weeks after the injection, LPP and histology of the urethral sphincter were evaluated. RESULTS: The VD + OVX group retained a decrease in LPP with sphincter muscle atrophy at least until 6 weeks after injury. The LPP and urethral sphincter muscle atrophy in the DFAT group recovered better than those in the fibroblast group. CONCLUSIONS: The persistence SUI model was created by a combination of VD and bilateral OVX in rats. Urethral injection of DFAT cells inhibited sphincter muscle atrophy and improved LPP in the persistence SUI model. These findings suggest that the DFAT cells may be an attractive cell source for cell-based therapy to treat SUI.

Tension-free vaginal mesh surgery versus laparoscopic sacrocolpopexy for pelvic organ prolapse: Analysis of perioperative outcomes using a Japanese national inpatient database.

OBJECTIVE: To compare nationwide outcomes of tension-free vaginal mesh surgery and laparoscopic sacrocolpopexy for the treatment of pelvic organ prolapse in Japan. METHODS: Using the Diagnosis Procedure Combination database, we collected data on female patients who underwent tension-free vaginal mesh surgery or laparoscopic sacrocolpopexy for pelvic organ prolapse from April 2014 to March 2015. We compared the proportion of perioperative adverse events, duration of anesthesia, total costs and postoperative length of stay between the groups. Univariate and multivariate analyses were carried out for age, comorbidity, mesh volume, additional concomitant surgery and hospital volume. RESULTS: We identified 3023 patients, including 2388 who underwent tension-free vaginal mesh surgery, and 635 who underwent laparoscopic sacrocolpopexy. The median age at the time of surgery was significantly higher in the tension-free vaginal mesh group (71 vs 66 years; P < 0.001). The tension-free vaginal mesh group had a higher proportion of all adverse events (7.1% vs 1.8%; P < 0.001) and a higher proportion of genitourinary complications (5.7% vs 1.1%; P < 0.001). The median duration of anesthesia was shorter in the tension-free vaginal mesh group (150 vs 286 min; P < 0.001). The total cost was significantly lower in the tension-free vaginal mesh group. CONCLUSIONS: Both procedures offer favorable results for surgical treatment of pelvic organ prolapse. Overall, the tension-free vaginal mesh procedure seems to represent a good option for high-risk women, such as elderly patients, whereas laparoscopic sacrocolpopexy is useful for younger patients with a higher level of sexual activity.

Clinical outcomes after IVF or ICSI using human blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum.

In this study the clinical and neo-natal outcomes after transfer of blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum (SER) were compared between IVF and intracytoplasmic sperm injection (ICSI) cycles. Clinical and neo-natal outcomes of blastocysts in cycles with at least one SER metaphase II oocyte (SER + MII; SER + cycles) did not significantly differ between the two insemination methods. When SER + MII were cultured to day 5/6, fertilization, embryo cleavage and blastocyst rates were not significantly different between IVF and ICSI cycles. In vitrified-warmed blastocyst transfer cycles, the clinical pregnancy rates from SER + MII in IVF and ICSI did not significantly differ. In this study, 52 blastocysts (27 IVF and 25 ICSI) derived from SER + MII were transferred, yielding 15 newborns (5 IVF and 10 ICSI) and no malformations. Moreover, 300 blastocysts (175 IVF and 125 ICSI) derived from SER-MII were transferred, yielding 55 newborns (24 IVF and 31 ICSI cycles). Thus, blastocysts derived from SER + cycles exhibited an acceptable ongoing pregnancy rate after IVF (n = 125) or ICSI (n = 117) cycles. In conclusion, blastocysts from SER + MII in both IVF and ICSI cycles yield adequate ongoing pregnancy rates with neo-natal outcomes that do not differ from SER-MII.

[A CASE OF URETEROUTERINE FISTULA AFTER CAESAREAN SECTION].

The reported incidence rate of iatrogenic ureteral injury is 0.5 to 3% among abdominal surgery. We report a case of ureterouterine fistula after caesarean section. A 38-year-old woman visited our department with a complaint of urinary incontinence without dry time after caesarean section. Several examinations revealed right ureterouterine fistula.Ureteroneocystostomy using psoas hitch and hysterectomy was performed. We found a firm adhesion and stitches around right lower ureter over the uterus, which lead to an additional hysterectomy. After surgery, urinary incontinence had improved. Following two years after surgery, we observed no urinary incontinence or renal dysfunction.

Transplantation of mature adipocyte-derived dedifferentiated fat cells for the treatment of vesicoureteral reflux in a rat model.

PURPOSE: Autologous cells potentially provide an ideal injectable substance for management in vesicoureteral reflux (VUR). The aim of this study is to examine the effects of mature adipocyte-derived dedifferentiated fat (DFAT) cell transplantation on VUR in a rat bladder pressurization-induced VUR model. METHODS: To create VUR, Sprague-Dawley rats underwent urethral clamping and placement of cystostomy followed by intravesical pressurization. Rat DFAT cells (1 × 106 cells, DFAT group, n = 5) or saline (control group, n = 5) was then injected into the bilateral vesicoureteral junctions. Two weeks later, VUR grade was evaluated on cystography. The number of apoptotic cells in the renal pelvic urothelium, the ureteral inner/outer diameter ratio and the area of connective tissue in the posterior bladder wall were measured. RESULTS: The reflux grade in the DFAT group was significantly lower than that in the control group. The number of apoptotic cells in the renal pelvic urothelium, ureteral inner/outer diameter ratio and connective tissue area in DFAT group were significantly lower in comparison with the control group. CONCLUSIONS: DFAT cell transplantation improved VUR and exerted nephroprotective effects in a rat VUR model.

Embryological outcomes in cycles with human oocytes containing large tubular smooth endoplasmic reticulum clusters after conventional in vitro fertilization.

There have been no studies analyzing the effect of large aggregates of tubular smooth endoplasmic reticulum (aSERT) after conventional in vitro fertilization (cIVF). The aim of this study was to investigate whether aSERT can be identified after cIVF and the association between the embryological outcomes of oocytes in cycles with aSERT. This is a retrospective study examining embryological data from cIVF cycles showing the presence of aSERT in oocytes 5-6 h after cIVF. To evaluate embryo quality, cIVF cycles with at least one aSERT-metaphase II (MII) oocyte observed (cycles with aSERT) were compared to cycles with normal-MII oocytes (control cycles). Among the 4098 MII oocytes observed in 579 cycles, aSERT was detected in 100 MII oocytes in 51 cycles (8.8%). The fertilization rate, the rate of embryo development on day 3 and day 5-6 did not significantly differ between cycles with aSERT and control group. However, aSERT-MII oocytes had lower rates for both blastocysts and good quality blastocysts (p < 0.05). aSERT can be detected in the cytoplasm by removing the cumulus cell 5 h after cIVF. However, aSERT-MII oocytes do not affect other normal-MII oocytes in cycles with aSERT.

Efficacy of transurethral prostate enucleation by bipolar system for patients with benign prostatic hyperplasia.

BACKGROUND: The aim of this paper was to evaluate the efficacies and safety of transurethral prostate enucleation by bipolar system (TUEB) for the patients with benign prostatic hyperplasia (BPH). METHODS: We prospectively evaluated clinical outcomes of TUEB in 55 patients with BPH from July 2005 to January 2011. Mean ages of the patients were 69.2 years. International Prostate Symptom Score (IPSS), IPSS-quality of life (IPSS-QOL) were assessed before and 12 months after surgery. Serum PSA, maximal flow rate (MFR), and post-void residual (PVR) were also evaluated before and 6 and 12 months after surgery. RESULTS: The median prostate volumes and resection volumes were 64.1 g (interquartile range [IQR]: 48-87) and 34.4 g (25-60.2), respectively. The median operation time was 138.0 min (100.2-169.2). Total IPSS scores and IPSS-QOL were significantly improved (from 24 [17-31] to 5 [2-8] points, and from 6 [5-6] to 2 [1-2] points, both P<0.001). MFR and PVR were significantly improved 6 and 12 months after TUEB (from 6.2 [3.9-8.3] to 15.1 [10.5-20.9], and 14.6 [10.2-20.5] mL/s, P<0.0001, and from 151.5 [81.5-284.7] to 16.5 [0-30.5], and 6.0 [0-41.0] mL, P<0.0001, respectively). Serum PSA also significantly decreased, 6 and 12 months (from 7.5 [4.7-9.8] to 1.1 [0.5-1.5], and 0.6 [0.3-1.9] ng/mL, P<0.0001). Although hemoglobin decreased after operation, no case experienced blood transfusion. Three episodes of urinary tract infections, 14 cases of mild stress urinary incontinence, 2 cases of urinary retention were occurred transiently with recovery within 1 month after surgery. CONCLUSIONS: We identified favorable efficacy and safety of TUEB. TUEB appears to be another possibility in the treatment of BPH.

Birth of nine normal healthy babies following transfer of blastocysts derived from human single-pronucleate zygotes.

PURPOSE: The purpose of this study is to examine the clinical outcomes of blastocysts derived from human single-pronucleate (1PN) embryos after conventional in vitro fertilization (cIVF) and intracytoplasmic sperm injection (ICSI) cycles. METHODS: This was a retrospective study at a reproductive center of a hospital. To evaluate embryo quality and clinical outcomes, cIVF or ICSI cycles with one or more 1PN embryos were compared with same cycles with 2PN embryos (control cycles). RESULTS: A total of 623 cycles (426 cIVF cycles and 197 ICSI cycles) were treated with cIVF or ICSI. The single pronuclear status rate was similar between cIVF (22.1 %) and ICSI (25.1 %) cycles. Although the development rates of 1PN embryos on day 3 and day 5/6 in cIVF were significantly higher than those in ICSI, those of 1PN embryos in cIVF were significantly lower compared to 2PN embryos (p < 0.01). Nonetheless, the ongoing pregnancy rates achieved with 1PN blastocysts in 1PN embryos did not significantly differ from the control group. Thirty-three transfer cycles with 33 blastocysts derived from 1PN embryos in cIVF resulted in nine deliveries with no newborn malformations; however, no implantation was observed in three ICSI cycles. CONCLUSION: Although the blastocyst formation rate of 1PN embryos was significantly lower than 2PN embryos in cIVF and ICSI cycles, 1PN blastocysts in cIVF, and not from ICSI, demonstrated an adequate ongoing pregnancy rate. These results suggested that 1PN blastocysts in cIVF are available for clinical use and may lead to an increase in the chance of pregnancy in patients receiving assisted reproductive technology with 1PN embryos.

Pyrrole-imidazole polyamide targeted to break fusion sites in TMPRSS2 and ERG gene fusion represses prostate tumor growth.

Aberrant overexpression of ERG induced by the TMPRSS2-ERG gene fusion is likely involved in the development of prostate cancer. Synthetic pyrrole-imidazole (PI) polyamides recognize and attach to the minor groove of DNA with high affinity and specificity. In the present study, we designed a PI polyamide targeting TMPRSS2-ERG translocation breakpoints and assessed its effect on human prostate cancer cells. Our study identified that this PI polyamide repressed the cell and tumor growth of androgen-sensitive LNCaP prostate cancer cells. Targeting of these breakpoint sequences by PI polyamides could be a novel approach for the treatment of prostate cancer.

Lower urinary tract symptoms in female patients with pelvic organ prolapse: efficacy of pelvic floor reconstruction.

OBJECTIVE: To evaluate the impact of pelvic floor reconstruction on lower urinary tract symptoms in patients with pelvic organ prolapse. METHODS: We carried out a prospective study at a single institution. A total of 223 female patients who underwent tension-free vaginal mesh surgery for pelvic organ prolapse between January 2006 and February 2010 were enrolled and prospectively evaluated. A total of 171 cases with concurrent stress urinary incontinence (76% of all cases) underwent concomitant transobturator tape sling. For evaluation of lower urinary tract symptoms, parameters included International Prostate Symptom Score, its quality of life score, International Consultation on Incontinence Questionnaires Short Form, overactive bladder questionnaire, maximal flow rate and postvoid residual. These parameters were evaluated at baseline, and at 3, 6 and 12 months after the surgery. RESULTS: The severity of International Prostate Symptom Score total scores significantly correlated with preoperative pelvic organ prolapse quantification stages, overactive bladder questionnaire total scores and International Consultation on Incontinence Questionnaires Short Form scores. A total of 37% of stage 4 showed ≥20 International Prostate Symptom Score (severe cases). Postvoid residual significantly increased in stage 4 compared with stage 2. Tension-free vaginal mesh improved International Prostate Symptom Score, overactive bladder questionnaire and International Consultation on Incontinence Questionnaires Short Form significantly, and also achieved grade 0 pelvic organ prolapse quantification in 91% of all cases at 1 year after surgery. Postvoid residual values significantly improved and remained stable for 1 year. Worse overactive bladder questionnaire score was a significant predictive factor for poor postoperative International Prostate Symptom Score. CONCLUSION: The tension-free vaginal mesh plus transobturator tape procedure improves lower urinary tract symptoms in the majority of patients presenting pelvic organ prolapse.

A case of solitary fibrous tumor of the kidney: an immunohistochemical and ultrastructural study with a review of the literature.

A solitary fibrous tumor (SFT) is an unusual spindle cell neoplasm that usually arises in the pleura but rarely occurs in the kidney. Despite its rarity, histological diagnosis of SFT is crucial to avoid misdiagnosis with other malignant tumors in the kidney. We report a SFT of the left kidney that presented as a malignant tumor on radiographic findings in a 75-year-old Japanese woman. The tumor was well circumscribed and composed of a mixture of spindle cells and dense collagenous bands with no areas of necrosis or cystic changes noted macroscopically or microscopically. Electron microscopy showed fibroblast-like cells with well-developed rough endoplasmic reticulum, surrounded with collagen fibers. Immunohistochemistry revealed reactivity for vimentin, CD34, Bcl-2, and CD99, but no staining for cytokeratin, S-100, desmin, actin, D2-40, or epithelial membrane antigen (EMA). These findings were compatible with those of SFT. Although SFT of the kidney is extremely rare, this tumor must be included in the differential diagnosis when we encounter renal tumors consisting of mesenchymal elements. Immunohistochemical study is the key to diagnosis for SFT, and ultrastructural study is useful for its diagnosis.

Medium without ammonium accumulation supports the developmental competence of human embryos.

L-Glutamine has been shown to play an important role during in vitro culture of mammalian embryos. However, it is easily decomposed into ammonium, which is believed to have deleterious effects on preimplantation embryos. In this study, we assessed prospectively the developmental competence of human embryos cultured in medium containing L-glutamine or a novel stable glutamine derivative and vitamins. The subjects of this study were 41 women who underwent IVF/ET treatment from September to November 2006 and from whom 6 or more oocytes were retrieved. Sibling oocytes were randomly divided into EA/BA (EmbryoAssyst and BlastAssyst containing a novel stable glutamine derivative and vitamins), and BAS groups (BlastAssyst system containing L-glutamine). There was no difference in pronuclear formation rate between EA/BA and BAS (74 vs. 69%). The blastulation rates of embryos based on the number of zygotes cultured in EA/BA on Days 5 (Day 0=insemination, 54%) and 6 (63%) were significantly higher (P<0.05) than those cultured in BAS (Day 5: 33% and Day 6: 45%, respectively). The present data indicate that a medium containing a novel stable glutamine derivative and vitamins supports the developmental competence of human embryos.

Effect of aspiration vacuum on the developmental competence of immature human oocytes retrieved using a 20-gauge needle.

In-vitro maturation (IVM) of immature oocytes has been proposed as a potential alternative to conventional IVF treatment following ovarian stimulation. However, the effects of the oocyte retrieval conditions on subsequent development have not been well understood. This study assessed the effects of different aspiration vacuums during oocyte retrieval on the developmental competence of immature oocytes following IVM, IVF and embryo transfer, retrospectively. Immature oocytes were aspirated with 20-gauge needles with a vacuum of 180 or 300 mmHg. Immature oocytes were cultured in IVM medium for 26 h. All mature oocytes were inseminated by intracytoplasmic sperm injection (ICSI). Embryo transfer was carried out 2 or 3 days after ICSI. The percentage of cumulus-cell enclosed oocytes and of transferable embryos per retrieved oocytes in 180 mmHg (69.7% and 23.8%, respectively) were significantly higher (P < 0.01) than those in 300 mmHg (46.2% and 12.8%, respectively). The ongoing pregnancy rate per retrieval cycle in 180 mmHg (30%) was higher (P < 0.01) than that in 300 mmHg (4.3%). The data indicate that lower pressure of vacuum aspiration with a 20-gauge needle improves the developmental competence of immature oocytes following IVM, IVF and embryo transfer.

Successful monozygotic twin delivery following in vitro maturation of oocytes retrieved from a woman with polycystic ovary syndrome: case report.

The incidence of monozygotic twinning (MZT) appears to be increasing within the field of assisted reproductive technology (ART), although the factors contributing to the phenomenon are still far from being identified. On the contrary, in vitro maturation (IVM) of oocytes is becoming more accepted and more and more babies have been born worldwide using this procedure. Assessing its safety and impact on monozygotic twinning (MZT), and following up the health of these babies, is essential. We report here a first case of successful monozygotic (MZ) twin delivery following IVM. The patient was a 28-year-old Japanese female, referred to the IVF clinic for primary infertility. Several previous cycles of ovarian stimulation had resulted in ovarian hyperstimulation syndrome (OHSS). The patient received norethisterone-mestranol to initiate the menstruation, and oocyte retrieval was performed 36 h after hCG. A total of 22 immature oocytes were obtained. Following incubation for 24 h in IVM medium, 50% of the oocytes were matured to the metaphase II (MII) stage. Nine oocytes were fertilized after ICSI with the husband's sperm. Three day 3 embryos were transferred into the uterus on the fourth day following oocyte retrieval. Three weeks after embryo transfer, a single gestational sac was visualized in the uterus. At 7 weeks of gestation, two fetal poles with cardiac activity were seen in the single gestational sac. Serial ultrasound examinations revealed a MZ, monochorionic diamniotic pregnancy. After intensive perinatal monitoring, two healthy male infants were delivered by Caesarean section at 35 weeks of gestation.

Freeze-thaw programmes rescue the implantation of day 6 blastocysts.

The developmental rate of a blastocyst is considered one of the main estimates for evaluating the implantation potential of embryos. Day 6 blastocysts have been reported to be much less viable than day 5 blastocysts. Regarding implantation, the implantation window is advanced due to a background of high sex hormones, and slower growing embryos may not implant because of possible desynchrony with the implantation window. The aim of this study was to investigate the efficacy of cryopreservation of such embryos and subsequent synchronization of embryo transfer with endometrial status. The results of 122 day 6 blastocysts transferred in the clinic were retrospectively examined. Pregnancy rates were compared between the stimulation cycle and hormone replacement cycle in terms of the method of endometrial preparation. Fifty-five day 6 blastocysts were transferred onto the stimulation cycle endometrium in 37 women, resulting in a 5.5% viable pregnancy rate. On the other hand, 67 day 6 blastocysts were transferred onto endometrium prepared by exogenous hormones in 40 women, resulting in a 26.9% viable pregnancy rate (P < 0.01). Consequently, the difference was highly significant. In conclusion, synchronous transfer of slow-growing embryos using the freeze-thaw technique contributes to a positive outcome.

Possible antenatal and perinatal related factors in development of cystic periventricular leukomalacia.

Cystic periventricular leukomalacia (cPVL), the principal ischemic brain injury in premature infants, is characterized by necrosis of the white matter in the periventricular region and the major neuropathology for spastic motor deficits in cerebral palsy or epilepsy. Recent reports strongly suggest that the brain injury associated with cPVL may have already occurred in utero. In this study we searched retrospectively for possible clinical situations related to cPVL to facilitate assessment of optimal management. A total of 201 babies born at gestational ages from 24 to 33 weeks were entered into the study (1992-1997) and examined for involvement of 18 factors in cPVL retrospectively. And psychomotor development was examined at least until 18 months of corrected age. Among 201 premature babies 35 cases were diagnosed as cPVL later developed spastic diplegia. There are 23 cases of preeclampsia, no infant suffering from cPVL. In the univariate analysis, exposure to antenatal indomethacin, cord length > or =40 cm, and a low Apgar score were significantly associated with a 2-3 risk increased of cPVL occurrence, while antenatal magnesium sulfate reduced the risk. Chorioamnionitis was positively correlated with the risk, but did not reach statistical significance. In the multivariate analysis we found the statistical significance in exposure to antenatal indomethacin, a low Apgar score, and antenatal magnesium sulfate. Our results suggested that preeclampsia and antenatal exposure of magnesium sulfate reduced the risk while antenatal exposure of indomethacin and low Apgar score associated with the occurrence of cPVL. These findings support a growing consensus that cPVL is often the result of maternal and fetal factors as well as antenatal treatment.

Effects of estradiol administration on feto-placental growth in rat.

BACKGROUND: To clarify the effect of estradiol benzoate on placental structure and its consequences for fetal survival and fetoplacental growth. STUDY DESIGN: Estradiol benzoate (0, 0.1, 1, 10, 100 microg/day) was infused intraperitoneally into pregnant Wistar rats from 12 to 19 days' gestation. Survival rate, weight of pups and placentas at 20 days' gestation, and plasma levels of estrogen and progesterone were measured. Pathological changes in the placenta were also examined. RESULTS: Estradiol benzoate reduced fetal survival (1 microg/day: 100%, 10 microg/day: 70%, 100 microg/day: 14.6%) and the weights of the pups and placentas in a dose-dependent manner. Maternal estradiol concentration was raised 23-fold with 100microg/day of estradiol benzoate. Trophoblast degeneration, including apoptosis and destruction of placental labyrinth was induced but the structures of the maternal kidney and liver were not affected. CONCLUSIONS: In pregnant rats, estradiol benzoate causes fetal mortality at a pharmacological dose (more than 10 microg/day) and fetoplacental growth retardation via trophoblastic degeneration and destruction of the placental labyrinth even at a physiological dose (1 microg/day).

Hypertension and angiotensin II hypersensitivity in aminopeptidase A-deficient mice.

Local concentrations of the vasopressor peptide, angiotensin II (AngII), depend upon the balance between synthesis and degradation. Previous studies of blood pressure (BP) regulation have focused primarily on the generation of AngII and its receptors, and less attention has been devoted to angiotensin degradation. Aminopeptidase A (APA, EC 3.4.11.7) is responsible for the N-terminal cleavage of AngII, a hydrolytic event that serves as a rate-limiting step in angiotensin degradation. To evaluate the physiological role of APA, we examined BP homeostasis in APA-deficient mice. We measured basal BP and BP with continuous infusion of AngII in APA mutant mice by tail-cuff method. We also evaluated the development and histology of AngII-targeted organs as well as urine excretion in these mice. Homozygous APA mutant mice were found to have elevated basal systolic BP when compared with heterozygous mutant and wild-type littermate mice. Infusion of AngII led to an enhanced systolic BP response in the APA-deficient mice. Despite the sustained elevation of BP in APA knockout mice, neither their renal and cardiac sizes nor their histological appearances were not different from control mice. Moreover, the volume, osmolality, and electrolyte content of the urine were normal in APA-deficient mice. APA deficiency increased baseline BP and enhanced the hypertensive response to increased levels of AngII. These findings indicate a physiological role for APA in lowering BP and offer novel insight into the mechanisms for developing hypertension.

Successful pregnancy after bromocriptine therapy in an anovulatory woman complicated with ovarian hyperstimulation caused by follicle-stimulating hormone-producing plurihormonal pituitary microadenoma.

Gonadotropin-producing pituitary adenomas are extremely rare in reproductive-age women. We report here a case of gonadotroph microadenoma with ovarian hyperstimulation. It was found in a 29-yr-old infertile Japanese woman with enlarged multicystic ovaries. The patient had an elevated basal serum estradiol level (up to 6755 pM, or 1840 pg/ml). Serum FSH and prolactin were mildly elevated (15.4 IU/liter, 1.4 nM or 31.4 ng/ml), whereas LH was low (0.5 IU/liter). The FSH level was paradoxically elevated in response to TRH administration. Dynamic magnetic resonance imaging revealed a pituitary microadenoma. Daily administration of bromocriptine, a dopamine agonist, normalized the ovarian size, and the patient ovulated naturally. She conceived after 3 months of bromocriptine therapy and delivered a normal child. She underwent elective transsphenoidal pituitary surgery, 3 yr after the delivery. Immunostaining of the resected tumor showed that 80% and less than 5% of the tumor cells stained for FSH-beta and prolactin, respectively. Furthermore, RT-PCR suggested that dopamine type 2 receptor was expressed in the adenoma. Gonadotroph microadenoma should be considered in women with spontaneous ovarian hyperstimulation, even if they have no neurological symptoms or marked pituitary enlargement. In such cases, bromocriptine therapy may be an alternative to pituitary surgery.

Dual renin-angiotensin blockade therapy in patients at high risk of early ovarian hyperstimulation syndrome receiving IVF and elective embryo cryopreservation: a case series.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an important and dangerous aspect of assisted reproduction techniques. Although elective cryopreservation of all embryos can prevent pregnancy-induced late OHSS, it cannot prevent early OHSS, which is induced by hCG administration. METHODS: We undertook this trial to assess the efficacy with which the combined oral administration of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) could prevent early OHSS in IVF patients at very high risk for this syndrome. Four women, who had serum estradiol concentration > or =8000 pg/ml on the day of hCG injection, were treated with the combination of the ACEI alacepril and the ARB candesartan cilexetil for 8 days starting the day after oocyte retrieval. Embryos were cryopreserved and embryo transfer was postponed until later cycles. RESULTS: Despite the extremely enlarged ovaries, no ascites was accumulated in any of the cases. Haematocrit (34.1 +/- 1.0) and serum albumin concentration (4.1 +/- 0.2 g/dl) were normal throughout the treatment period. These patients showed elevated plasma renin and angiotensin II concentration before the treatment. CONCLUSIONS: The dual renin-angiotensin blockade therapy used here would be worth exploring further in a study with more patients and a prospective, randomized design.