Henry Bohler

Adipose tissue and reproduction in women

Adipose tissue has been viewed as the primary source of stored energy, but with the discovery of novel adipose tissue gene products, i.e., adipokines, another equally important role has emerged. Adipose tissue is a key endocrine organ involved in multiple processes, including glucose homeostasis, steroid production, immunoregulation, hematopoesis, and reproduction. The distribution of adipose tissue may also have a significant impact on reproductive function.

Dysregulation of leptin and testosterone production and their receptor expression in the human placenta with gestational diabetes mellitus.

Whether the placenta contributes to some of the abnormal hormonal profiles in gestational diabetes mellitus (GDM) pregnancies and whether GDM affects placental endocrine signaling pathways are yet to be established. The objective of this study was to investigate differences in the expression of the placental steroid and peptide hormone synthesis-related factors, enzymes and their receptors between normal and GDM pregnancies. Nine term placentae from GDM pregnancies and twelve from healthy pregnancies were collected. The results of immunohistochemistry, Western blotting and semiquantitative RT-PCR indicated that mRNA and protein levels of leptin, leptin receptors, androgen receptor and FGF2 were significantly higher in the GDM placentae than non-GDM placentae; while NRIH3, NRIH2, StARD3, CYP11A1, HSD3B, HSD11B, HSD17B, ERalpha, ERbeta, progesterone receptor, FGF receptor-2, insulin receptor-alpha and -beta showed no differences. Interestingly, Western blotting and immunohistochemistry revealed that aromatase protein concentrations in the GDM placentae were significantly reduced without a change in mRNA levels. Moreover, androgen upregulated FGF2 expression in the placental villous explants. These findings suggest that the placentae of GDM pregnancies contribute to elevated testosterone and leptin levels due to a decrease in the conversion of testosterone to estrogens and to an increase in leptin production. The androgen and leptin signaling pathways may be over-activated by the presence of excessive ligands and overexpressed receptors in GDM placentae. Dysregulation of these two endocrine networks may contribute to placental abnormalities eventually increasing the frequency of maternal and fetal complications associated with GDM.

Live birth following in vitro maturation of oocytes retrieved from extracorporeal ovarian tissue aspiration and embryo cryopreservation for 5 years

OBJECTIVE To report a live birth after in vitro maturation (IVM) of oocytes retrieved from extracorporeal ovarian tissue aspiration in the setting of fertility preservation. DESIGN Observational study. SETTING Academic center. PATIENT(S) A 23-year-old woman. INTERVENTION(S) IVM from extracorporeal ovarian tissue aspiration. MAIN OUTCOME MEASURE(S) Live birth after IVM. RESULT(S) A 23-year-old woman conceived with embryos derived from extracorporeal oocyte aspiration followed by IVM, embryo freezing, and frozen embryo transfer. CONCLUSION(S) A healthy live birth from extracorporeal aspiration of immature oocytes, IVM, and a frozen embryo transfer after 5 years was documented. Consideration of this technique should be made as a primary or adjunct intervention in the setting of fertility preservation.

Age and a single day-14 β-HCG can predict ongoing pregnancy following IVF

The current study was undertaken to investigate the use of beta human chorionic gonadotrophin (beta-HCG) concentration and other significant factors to predict the likelihood of an IVF pregnancy progressing to detection of cardiac activity by ultrasound, and to create data tables which can be used for patient counselling. A retrospective data analysis was undertaken of 1374 IVF cycles performed from January 1997 to July 2007, resulting in 662 pregnancies. Maternal age (P = 0.0005), day-14 (P < 0.001) and day-16 (P < 0.001) post-oocyte aspiration beta-HCG concentrations were found to be significant in predicting pregnancy outcome. Multiple logistic regression modelling revealed that the most accurate predictive model used a single day-14 beta-HCG concentration and maternal age. Day-14 and day-16 beta-HCG concentrations were highly correlated, with the addition of a day-16 concentration adding no additional predictive value. Ongoing pregnancy rates were proportional to day-14 beta-HCG concentration and inversely proportional to maternal age. The multiple pregnancy incidence increased proportionally with the initial beta-HCG concentration. Thus, for the counselling of patients following IVF, a single day-14 post-oocyte-aspiration beta-HCG concentration and maternal age are most predictive of the pregnancy continuing to detection of cardiac activity by ultrasound.

Ggnbp2 Is Essential for Pregnancy Success via Regulation of Mouse Trophoblast Stem Cell Proliferation and Differentiation

ABSTRACT The Ggnbp2 null mutant embryos died in utero between Embryonic Days 13.5 to 15.5 with dysmorphic placentae, characterized by excessive nonvascular cell nests consisting of proliferative trophoblastic tissue and abundant trophoblast stem cells (TSCs) in the labyrinth. Lethality of Ggnbp2 null embryos was caused by insufficient placental perfusion as a result of remarkable decreases in both fetal and maternal blood vessels in the labyrinth. These defects were accompanied by a significant elevation of c-Met expression and phosphorylation and its downstream effector Stat3 activation. Knockdown of Ggnbp2 in wild-type TSCs in vitro provoked the proliferation but delayed the differentiation with an upregulation of c-Met expression and an enhanced phosphorylation of c-Met and Stat3. In contrast, overexpression of Ggnbp2 in wild-type TSCs exhibited completely opposite effects compared to knockdown TSCs. These results suggest that loss of GGNBP2 in the placenta aberrantly overactivates c-Met-Stat3 signaling, alters TSC proliferation and differentiation, and ultimately compromises the structure of placental vascular labyrinth. Our studies for the first time demonstrate that GGNBP2 is an essential factor for pregnancy success acting through the maintenance of a balance of TSC proliferation and differentiation during placental development.

Adipose-Derived Stromal Vascular Fraction Cell Effects on a Rodent Model of Thin Endometrium.

Endometrial dysfunction affects approximately 1% of infertile women, and there is currently no standard therapy for improving fertility treatment outcomes in these patients. In our study, we utilized a rodent model of thin endometrium to test whether intrauterine application of adipose-derived stromal vascular fraction cells (SVF) could improve morphological and physiological markers of endometrial receptivity. Using anhydrous ethanol, endometrial area and gland density were significantly reduced in our model of thin endometrium. Application of SVF was associated with a 29% reduction in endometrial vascular endothelial growth factor (VEGF) expression and significant increases in uterine artery systolic/diastolic velocity ratios and resistance index values, suggesting reduced diastolic microvascular tone. However, no significant improvements in endometrial area or gland density were observed following SVF treatment. 3D confocal imaging demonstrated poor engraftment of SVF cells into recipient tissue, which likely contributed to the negative results of this study. We suspect modified treatment protocols utilizing adjuvant estrogen and/or tail vein cell delivery may improve SVF retention and therapeutic response in subsequent studies. SVF is an easily-obtainable cell product with regenerative capability that may have a future role in the treatment of infertile women with endometrial dysfunction.

Successful increase in uterine volume and subsequent pregnancy in a patient with a history of radiation and chemotherapy

A 26-year-old woman with a history of cranial radiation and chemotherapy desired pregnancy. Pelvic ultrasound scanning demonstrated a small uterine volume of 7 mL. After 25 weeks of estrogen therapy, her uterine volume increased to 37 mL. The patient had an uncomplicated pregnancy with the use of donor oocytes and delivered a term healthy daughter.

Discourage the presurgical spray tan: Physicians were puzzled by the patient's postoperative skin damage

Krause. Discourage the presurgical spray tan. Am J Obstet Gynecol 2013. Case notes A 34-year-old woman underwent robotic-assisted lysis of adhesions, vaporization of endometriosis, and a myomectomy. She had a vague history of an allergic reaction to an unknown stimulus during anesthesia. The patient was prepped with 2% chlorhexidine gluconate and 70% isopropyl alcohol scrub (ChloraPrep; CareFusion Corp, San Diego, CA) for the abdomen and 10% povidone iodine preparation solution (Aplicare Inc, Meriden, CT) for the perineum and draped. After the operative procedure, we noted erythema and what appeared to be disruption of the deep dermal skin layer in areas where the adhesive tape had been applied. A noticeable contrast in skin pigmentation existed in the affected areas, raising further concern for skin damage and denudement (Figure). Bacitracin ointment was applied. Postoperatively, the patient revealed that she had undergone a spray tan 2 days before her operation. Consultation with a wound-care specialist confirmed that the spray tan had been removed in the areas where the adhesive tape was in direct contact with the skin. Although apoptotic layers may have been removed, the skin was intact.