M.E. Abdallah

Post-Essure Hysterosalpingography Compliance in a Clinic Population

STUDY OBJECTIVE To determine the follow-up rate for post-Essure hysterosalpingography (HSG) in a non-study, general clinic population in an urban environment. DESIGN Retrospective chart review (Canadian Task Force classification II-2). SETTING University teaching hospital. PATIENTS Eighty-three University Health Center (UHC) patients who underwent attempted placement of the Essure permanent birth control device at the ambulatory surgery center at Hutzel Womens Hospital from January 2003 through June 2007. INTERVENTION Hysteroscopic placement of the Essure permanent birth control device. MEASUREMENTS AND MAIN RESULTS Placement of the Essure permanent birth control device was attempted in 83 patients, of which 79 were successfully completed (95.2%). Of the 79 patients, 10 underwent post-Essure HSG (12.7%). HSG was performed 3 to 6 months after placement of the Essure device. Bilateral tubal occlusion was documented in all 10 patients. CONCLUSION Despite preoperative and postoperative counseling, the follow-up rate for post-Essure HSG for this clinic population was only 12.7%. For those in whom HSG was performed, bilateral tubal occlusion was confirmed in all. Steps or approaches to promote compliance with postprocedural confirmation of tubal occlusion should be utilized to improve future follow-up rates.

Trends in Sterilization since the Introduction of Essure Hysteroscopic Sterilization

STUDY OBJECTIVE To investigate trends in sterilization in women at the Detroit Medical Center, Michigan (DMC), since the introduction of Essure hysteroscopic sterilization. DESIGN Retrospective study (Canadian Task Force classification II-2). SETTING Outpatient surgery center and university teaching hospitals. PATIENTS Women who underwent interval sterilization procedures at the DMC (Hutzel Womens Hospital, Sinai-Grace Hospital, and the Berry Center) and postpartum sterilization procedures at Hutzel Womens Hospital between January 1, 2002, and December 31, 2007. INTERVENTIONS Permanent sterilization procedures including minilaparotomy tubal ligation, laparoscopic sterilization, Essure hysteroscopic sterilization, and postpartum tubal ligation performed at the time of cesarean section or after vaginal delivery. MEASUREMENTS AND MAIN RESULTS In all, 5509 permanent sterilization procedures were performed in the 6 years between January 1, 2002, and December 31, 2007, at the DMC facilities analyzed: 2484 interval sterilization procedures at Hutzel Womens Hospital, Sinai-Grace Hospital, and the Berry Center, and 3025 postpartum tubal ligations at Hutzel Womens Hospital. From 2002 through 2007, the decrease in laparoscopic sterilizations from 97.9% to 48.5% of all interval sterilization procedures corresponded significantly with the increase in Essure hysteroscopic sterilizations from 0.0% to 51.3% (p <.001). Postpartum tubal ligations performed after vaginal delivery also decreased significantly during the study period from 7.9% to 3.3% of all vaginal deliveries (p <.001) while the percentage of tubal ligations performed at the time of cesarean section remained constant (p =.051). CONCLUSION At the DMC facilities analyzed from January 1, 2002, through December 31, 2007, a significant decrease occurred in the percentage of laparoscopic sterilizations and postpartum tubal ligations performed after vaginal delivery. Of the interval sterilizations performed, the percentage of Essure hysteroscopic sterilizations increased significantly from 0.0% to 51.3% of all procedures. Since the approval of Essure hysteroscopic sterilization in November 2002, this minimally invasive method of hysteroscopic sterilization has increased in popularity at the DMC.

Cellular stress causes reversible, PRKAA1/2-, and proteasome-dependent ID2 protein loss in trophoblast stem cells

Stress reduces fertility, but the mechanisms mediating this are not understood. For a successful pregnancy, placental trophoblast stem cells (TSCs) in the implanting embryo proliferate and then a subpopulation differentiates to produce hormones. Normally, differentiation occurs when inhibitor of differentiation 2 (ID2) protein is lost in human and mouse placental stem cells. We hypothesize that stress enzyme-dependent differentiation occurs in association with insufficient TSC accumulation. We studied a well-defined model where TSC differentiation requires ID2 loss. The loss of ID2 derepresses the promoter of chorionic somatomammotropin hormone 1 (CSH1), the first hormone after implantation. Csh1 mRNA is known to be induced in stressed TSCs. In this study, we demonstrate that AMP-activated protein kinase (PRKAA1/2, aka AMPK) mediates the stress-induced proteasome-dependent loss of ID2 at high stress levels. At very low stress levels, PRKAA1/2 mediates metabolic adaptation exemplified by the inactivation of acetyl coA carboxylase by phosphorylation without ID2 loss. At the highest stress levels, irreversible TSC differentiation as defined by ID2 loss and slower cell accumulation occurs. However, lower stress levels lead to reversible differentiation accompanied by metabolic adaptation. These data support the hypothesis that PRKAA1/2 mediates preparation for differentiation that is induced by stress at levels where a significant decrease in cell accumulation occurs. This supports the interpretation that enzyme-mediated increases in differentiation may compensate when insufficient numbers of stem cells accumulate.

Conservative management of cervical ectopic pregnancy: utility of uterine artery embolization

OBJECTIVE To evaluate the use of uterine artery embolization (UAE) in conjunction with methotrexate in the conservative treatment of cervical ectopic pregnancy (CEP). DESIGN Case series. SETTING Tertiary-care university hospital. PATIENT(S) Cases of CEP treated at Hutzel Womens Hospital between January 1997 and December 2008. INTERVENTION(S) Multidose methotrexate treatment with or without UAE and intra-amniotic potassium chloride injection (KCl). MAIN OUTCOME MEASURE(S) Beta-human chorionic gonadotropin level, vaginal bleeding, length of hospital stay, and future fecundity. RESULT(S) A retrospective analysis of 15 patients with CEP treated conservatively using methotrexate with leucovorin rescue (MTx/Leu) alone (group 1, five cases), with UAE as an adjunctive therapy (group 2, six cases), or also having received intra-amniotic KCl before UAE (group 3, four cases) is reported. There was no significant difference in age, parity, or gestational age among treatment groups. The median β-hCG level on presentation was 9,606 mIU/mL for group 1, 26,516 mIU/mL for group 2, and 130,464 mIU/mL for group 3. The difference was found to be statistically significant. No patients developed complications from UAE. Of the 10 patients who underwent UAE, 2 subsequently had confirmed viable pregnancies. CONCLUSION(S) Uterine artery embolization with methotrexate is an option for minimally invasive intervention in the treatment of CEP.

Benzo(a)pyrene causes PRKAA1/2‐dependent ID2 loss in trophoblast stem cells

Benzo(a)pyrene (BaP), a cigarette smoke component, is metabolized to diol esters (BPDE) that bind to DNA and form mutagenic BPDE‐DNA adducts. BaP activates stress enzymes including stress‐activated protein kinase/jun kinase (MAPK8/9) in embryos, AMP‐activated protein kinase alpha1/2 subunits (PRKAA1/2) in somatic cells, and inhibits the proliferation of trophoblast cell lineages. The loss of transcription factor inhibitor of differentiation (ID)2 is required for the initial differentiation of mouse trophoblast stem cells (TSC) in implanting mouse embryo to produce the first placental hormone, chorionic sommatomammotropin (CSH)1. Here we demonstrate that BaP activates PRKAA1/2 and causes ID2 protein loss in TSC in a time‐ and dose‐dependent manner. Although PRKAA1/2 was activated at low BaP doses, PRKAA1/2‐dependent ID2 protein loss occurred at a dose that was similar to the threshold that results in a significant decrease in TSC accumulation and decreased fraction of proliferating TSC. This suggests a possible relationship between stress‐induced declines in cell accumulation and stem cell differentiation when BaP levels are high. The threshold BaP dose that induces significant ID2 loss is in the range of a 2–3 pack/day habit, suggesting that this mechanism may be involved with implantation failure in smoking women. Mol. Reprod. Dev. 77: 533–539, 2010.

Massive subchorionic hematomas following thrombolytic therapy in pregnancy

BACKGROUND: Medical therapy for thrombosed valve in pregnancy has become an acceptable alternative to surgery, especially in hemodynamically compromised patients. Placental changes after thrombolytic therapy have rarely been reported. CASES: Sonograms were done within 24 hours after administration of thrombolytic agents at 15 and 26 weeks of gestation, respectively, in 2 women whose pregnancies were complicated with thrombosis of prosthetic mitral valves. Both patients developed massive subchorionic hematomas, which persisted in 1 patient who underwent cesarean delivery at 34 weeks of gestation for cardiac indications (Apgar scores 9 and 10 at 1 minute and 5 minutes, respectively). The hematomas resolved in the other patient, who delivered at term. CONCLUSION: Massive subchorionic hematomas may be observed in patients after thrombolytic therapy. Other reports are needed to establish whether such placental findings are common lesions after such therapy and to determine their impact on pregnancy outcome.

The Effect of Paternal Age on Outcome in Assisted Reproductive Technology Using the Ovum Donation Model

Objective: To determine the effect of paternal age (PA) on implantation and live birth rates in an ovum donation program. Design: Retrospective study. Methods: A total of 237 ovum donor cycles were reviewed. All donors were stimulated with gonadotrophin-releasing hormone agonist (GnRHa) downregulation and human menopausal gonadotropin. Recipients were prepared with GnRHa downregulation and estradiol/progesterone replacement. Embryo transfers were done at blastocyst stage under ultrasound guidance. The effect of PA on outcome was analyzed controlling for number and grade of embryos transferred. Outcome was not pregnant (NP), spontaneous abortion (SAb), and live births (LBs). Results: Of the 237 cycles, 36 resulted in NP (15.2%), 39 in SAb (16.5%), and 162 in LB (68.4%). The mean PA (MPA) was significantly different between the 3 groups, and implantation rates also declined with increasing MPA (P =.01). Overall, the mean number and grade of embryos transferred were 2.1 ± 0.4 and 1.3 ± 0.4, respectively. The NP couples had more embryos of poorer grade than SAb and LB couples (P <.05), but there were no differences between SAb and NP couples (P >.85). Logistic regression analysis demonstrated a 26% lower odds of live birth rate with each 5-year increase in PA (P =.01). Conclusions: Advanced PA has an adverse impact on assisted reproductive technology (ART) outcome. After adjusting for number and embryo grades transferred, a younger PA has a more favorable ART outcome.

Eomesodermin, HAND1, and CSH1 proteins are induced by cellular stress in a stress-activated, protein kinase-dependent manner

Eomesodermin (Eomes) is a transcription factor essential for trophoblast development. Stress stimuli activate stress‐activated protein kinase (MAPK8/9) and modulate transcription factors in trophoblast stem cells (TSC). In this study, we test the hypothesis that stress‐induced Eomes upregulation and downstream trophoblast development are MAPK8/9‐dependent. Immunocytochemical and immunoblot assays suggest that Eomes is induced by hyperosmolar stress in a dose‐ and time‐dependent manner. Two MAPK8/9 inhibitors that work by different mechanisms, LJNKl1 and SP600125, block induction of Eomes protein by stress. During normal TSC differentiation, the transcription factor heart and neural crest derivatives expressed 1 (HAND1) is dependent on Eomes, and chorionic somatomammotropin hormone 1 (CSH1) expression is dependent on HAND1. Similar to Eomes, HAND1 and CSH1 induction by stress are MAPK8/9‐dependent, and CSH1 is induced in nearly all stressed TSC. CSH1 induction normally requires downregulation of the transcription factor inhibitor of differentiation 2 (ID2) as well as HAND1 upregulation. It was shown previously that hyperosmolar stress induces AMP‐activated protein kinase (PRKAA1/2)‐dependent ID2 loss in a MAPK8/9‐independent manner. Inhibition of PRKAA1/2 with compound C and LJNKl1, more than MAPK8/9 inhibitors alone, inhibits the induction of CSH1 by stress. Taken together these data suggest that stress‐induced MAPK8/9 and PRKAA1/2 regulate transcription factors Eomes/HAND1 and ID2, respectively. Together this network mediates induction of CSH1 by stress. Therefore, stress triggers a proportional increase in a normal early TSC differentiation event that could be adaptive in inducing CSH1. But the flexibility of TSC to undergo stress‐induced differentiation could lead to pathophysiological consequences if stress endured and TSC differentiation became unbalanced. Mol. Reprod. Dev. 78:519–528, 2011.

Sequential use of thrombolytic agents for thrombosed mitral valve prosthesis during pregnancy.

Abstract Thrombolytic therapy has gained popularity as an alternative to surgery in the treatment of prosthetic heart valve thrombosis.We report on the sequential use of streptokinase followed by recombinant tissue type plasminogen activator (rt-PA) for the treatment of a thrombosed prosthetic mitral valve in a pregnant woman at 26 weeks of gestation. Although thrombolysis was unsuccessful, the patient carried till 34 weeks of gestation and delivered by cesarean section a live newborn with an uneventful postpartum course. Based on our case and on what has been previously described in the literature, thrombolytic therapy should be considered as an option in the management of hemodynamically unstable pregnant patients with prosthetic valve thrombosis.When a single agent proves insufficient, combination therapy should be considered as it might provide hemodynamic stability and improvement in cardiac function that would allow patients at a high surgical risk to carry their pregnancy to viability.

The role of hysteroscopic biopsy in obtaining specimens for cytogenetic evaluation in missed abortion prior to suction dilatation and curettage.

Aim:To estimate whether hysteroscopic-guided biopsy of gestational sac(s) in first trimester missed abortion increases the sensitivity of detecting aneuploidy compared to washing and careful specimen collection after suction dilatation and curettage (D&C). Materials and Methods:Thirty-five patients with first trimester missed abortion of which 25 underwent 29 suction D&Cs and 10 underwent hysteroscopic-guided biopsy of 12 gestational sacs prior to suction D&C. The karyotype of products of conception specimens were analyzed by G-banding techniques. Results:The percentage of specimens with 46,XX, 46,XY and aneuploidy were not significantly different in the hysteroscopic group [4/12 (33.3%), 3/12 (25.0%) and 5/12 (41.7%)] compared with the D&C group [8/29 (27.6%), 5/29 (17.2%) and 16/29 (55.2%)]. Although parity differed significantly between groups, it did not hold in a multivariable logistic regression model built to estimate whether the parity, gestational age and specimen collection method predict the likelihood of detecting a 46,XX chromosomal complement. Conclusions:Direct hysteroscopic-guided biopsies of gestational sac(s) do not increase the sensitivity of conventional cytogenetics for detecting aneuploidy when compared to specimens obtained by washing and microscopic identification of villi or fetal tissue after suction D&C.