Controversies in the management of hypothyroidism during pregnancy.

IMPORTANCE: In the last 3 years, we have witnessed the publication of multiple but conflicting guidelines on the management of hypothyroidism during pregnancy. Hypothyroidism is one of the most common endocrinopathies in reproductive-age and pregnant women. Given the prevalence of thyroid disease, it is highly likely that obstetricians will encounter and provide care for pregnant women with thyroid disease. Therefore, a review of current guidelines and management options is clinically relevant. OBJECTIVES: Our goals are to review the changes in thyroid function during pregnancy, the options for testing for thyroid disease, the different categories of thyroid dysfunction and surveillance strategies among subspecialty societies, and the obstetric hazards associated with thyroid dysfunction and review the evidence for benefit of treatment options for thyroid disease. EVIDENCE ACQUISITION: We reviewed key subspecialty guidelines, as well as current and ongoing studies focused on the treatment of hypothyroidism during pregnancy. RESULTS: There are significant differences in the identification and management of thyroid disease during pregnancy among subspecialists. We present our recommendations based on the available evidence. RELEVANCE: Evidence exists that obstetricians struggle with the diagnosis and treatment of hypothyroidism. According to recent surveys, the management of hypothyroidism during pregnancy is the number 1 endocrine topic of interest for obstetricians. A synopsis of recently published subspecialty guidelines is timely. CONCLUSIONS: Recent, evidence-based findings indicate that obstetricians should consider modifying their approach to the identification and treatment of thyroid disease during pregnancy.

Precision of progesterone measurements with the use of automated immunoassay analyzers and the impact on clinical decisions for in vitro fertilization.

OBJECTIVE: To compare the precision of progesterone measurements obtained with the use of immunoassays and of liquid chromatography-tandem mass spectrometry (LC-MS/MS). DESIGN: Comparative study. SETTING: Academic, private practice, and in vitro fertilization (IVF) research centers. PATIENT(S): A total of 189 human serum samples were collected during controlled ovarian hyperstimulation and early pregnancy in women undergoing IVF. INTERVENTION(S): Serum progesterone pools (n = 10; 0.2-4 ng/mL) were sent to four laboratory centers that used four different automated immunoassay analyzers. Progesterone was measured by immunoassay in triplicate at three separate time points (n = 9 per pool) and by LC-MS/MS in triplicate once (n = 3 per pool). MAIN OUTCOME MEASURE(S): Inter- and intraassay coefficients of variation (CVs) of progesterone measurements were compared for each analyzer and LC-MS/MS. RESULT(S): Progesterone measurements by immunoassay were highly correlated with those by LC-MS/MS. Only two analyzers had intraassay CVs <10% at all three experimental time points, and only two analyzers had an interassay CV <10%. Mean progesterone levels by the analyzers were different across multiple progesterone pools. CONCLUSION(S): Our results indicate that progesterone threshold measurements used for IVF clinical decisions should be interpreted cautiously and based on laboratory- and method-specific data. A validated progesterone standard incorporated into daily immunoassays could improve medical decision accuracy.

Human embryonic stem cells derived by somatic cell nuclear transfer.

Reprogramming somatic cells into pluripotent embryonic stem cells (ESCs) by somatic cell nuclear transfer (SCNT) has been envisioned as an approach for generating patient-matched nuclear transfer (NT)-ESCs for studies of disease mechanisms and for developing specific therapies. Past attempts to produce human NT-ESCs have failed secondary to early embryonic arrest of SCNT embryos. Here, we identified premature exit from meiosis in human oocytes and suboptimal activation as key factors that are responsible for these outcomes. Optimized SCNT approaches designed to circumvent these limitations allowed derivation of human NT-ESCs. When applied to premium quality human oocytes, NT-ESC lines were derived from as few as two oocytes. NT-ESCs displayed normal diploid karyotypes and inherited their nuclear genome exclusively from parental somatic cells. Gene expression and differentiation profiles in human NT-ESCs were similar to embryo-derived ESCs, suggesting efficient reprogramming of somatic cells to a pluripotent state.

Assessment of the tracer delay effect in whole-brain computed tomography perfusion: results in patients without known neuroanatomic abnormalities.

OBJECTIVE: Whole-brain computed tomography perfusion (CTP) data sets generated by tracer delay-insensitive singular value decomposition plus (SVD+) and standard singular value decomposition (sSVD) deconvolution algorithms were evaluated to quantify relatedness and discrepancies in CTP results. METHODS: Twenty females with symmetrical hemispheric CTP maps indicative of brain tissue without apparent abnormalities were studied. Tissue-specific CTP values were analyzed. RESULTS: Standard SVD values were higher than SVD+ for cerebral blood flow. Other CTP values had minimal differences across brain regions. All simple linear regression models were statistically significant (P < 0.05) except for cerebral blood flow in white matter (P = 0.06). Cerebral blood volume had a good model fit, and mean transit time, a poor fit. CONCLUSIONS: Corresponding fitted CTP values for sSVD and SVD+ based on regression equations for brain-tissue types are presented. Additional research is required to compare SVD+ and sSVD in disease states when significant hemodynamic brain alterations are present.

Towards germline gene therapy of inherited mitochondrial diseases.

Mutations in mitochondrial DNA (mtDNA) are associated with severe human diseases and are maternally inherited through the egg's cytoplasm. Here we investigated the feasibility of mtDNA replacement in human oocytes by spindle transfer (ST; also called spindle-chromosomal complex transfer). Of 106 human oocytes donated for research, 65 were subjected to reciprocal ST and 33 served as controls. Fertilization rate in ST oocytes (73%) was similar to controls (75%); however, a significant portion of ST zygotes (52%) showed abnormal fertilization as determined by an irregular number of pronuclei. Among normally fertilized ST zygotes, blastocyst development (62%) and embryonic stem cell isolation (38%) rates were comparable to controls. All embryonic stem cell lines derived from ST zygotes had normal euploid karyotypes and contained exclusively donor mtDNA. The mtDNA can be efficiently replaced in human oocytes. Although some ST oocytes displayed abnormal fertilization, remaining embryos were capable of developing to blastocysts and producing embryonic stem cells similar to controls.

Dyspareunia and sexual dysfunction in women seeking fertility treatment.

OBJECTIVE: To compare rates of dyspareunia in infertile women and healthy controls. Secondary aims are to determine whether demographic characteristics, rates of sexual dysfunction, and baseline depression status differ between the two groups. DESIGN: A case-control study. SETTING: University-based faculty fertility and OB/GYN generalist clinics. PATIENT(S): Seventy-five infertile female subjects presenting to the infertility clinic and 210 women presenting to the generalist clinic for their annual exam. INTERVENTION(S): Completion of an anonymous survey including demographic information, the Female Sexual Function Index (FSFI), Patient-Health Questionnaire-9 (PHQ-9), and original questions regarding sexual pain. MAIN OUTCOME MEASURE(S): Rate of dyspareunia and sexual dysfunction. RESULT(S): There were no significant differences in rates of dyspareunia (37.6% controls vs. 30.7% study) or the rate of sexual dysfunction (31.9% controls vs. 37.3% study). Infertile women had more frequent intercourse than controls and were more likely to be married. There were otherwise no differences in baseline rates of depression, demographic characteristics, or individual domain scores of the FSFI. CONCLUSION(S): Women seeking fertility treatment had similar rates of dyspareunia and sexual dysfunction compared with controls.

Thoracic endometriosis unmasked by ovarian hyperstimulation for in vitro fertilization.

Thoracic endometriosis syndrome is a well-described, rare manifestation of endometriosis. We present a case of a 35-year old woman undergoing controlled ovarian stimulation prior to in vitro fertilization (IVF) who developed bilateral hemorrhagic pleural effusions. She was initially diagnosed with ovarian hyperstimulation syndrome, a complication of infertility therapy; however, she was later found to have occult thoracic endometriosis. We describe ovarian hyperstimulation syndrome and review the manifestations of thoracic endometriosis syndrome. Although endometriosis is a hormone-dependent disease, the rate of IVF complications related to endometriosis is low.

Changes in circulating levels and ratios of angiopoietins during pregnancy but not during the menstrual cycle and controlled ovarian stimulation.

OBJECTIVE: To determine whether angiopoietin (ANGPT)-1 and -2 are detectable in the circulation of nonhuman primates and women and whether these levels fluctuate in association with ovarian activity. DESIGN: Prospective. SETTING: National Primate Research Center, medical center, and infertility clinic. PATIENT(S): Adult female rhesus monkeys; 15 women donating oocytes for infertility treatment. INTERVENTION(S): Controlled ovarian stimulation with gonadotropins, removal of the corpus luteum and ovaries, oocyte retrieval, and ET. MAIN OUTCOME MEASURE(S): Circulating levels of ANGPT-1 and ANGPT-2. RESULT(S): Serum ANGPT-1 and ANGPT-2 levels were detectable and invariant in maintaining an ANGPT-1 to -2 ratio >1 in [1] macaques over the course of the natural menstrual cycle, during a controlled ovulation protocol, and after removal of the corpus luteum or ovaries and [2] women undergoing controlled ovarian simulation. In contrast, the ANGPT-1 to -2 ratio was markedly decreased (<<1) at mid-to-late gestation in macaques and in the follicular fluid of women undergoing controlled ovarian simulation because of increased levels of ANGPT-2. CONCLUSION(S): The ovary and its dominant structures are not major contributors to circulating levels of ANGPT-1 or ANGPT-2. The physiologic importance of the rising levels of ANGPT-2 after the luteal-placental shift in pregnancy is unknown.

Insulin and insulin-like growth factor stimulation of vascular endothelial growth factor production by luteinized granulosa cells: comparison between polycystic ovarian syndrome (PCOS) and non-PCOS women.

CONTEXT: Vascular endothelial growth factor A (VEGF-A) is a potent cytokine that promotes angiogenesis and vascular permeability. After controlled ovarian stimulation (COS) for in vitro fertilization (IVF), excessive VEGF-A production can occur, particularly in women with polycystic ovarian syndrome (PCOS); however, it is unclear whether the regulation of VEGF-A production is different between PCOS and non-PCOS women. OBJECTIVE: The aim of this study was to determine whether there were differences in the dose- and time-dependent effects of insulin and IGFs on VEGF-A production by luteinized granulosa cells (LGCs) from women with and without PCOS. DESIGN AND SETTING: A prospective comparative experimental study was conducted at an institutional practice. PATIENTS: Patients included six PCOS and six non-PCOS women undergoing COS and IVF. INTERVENTIONS: Interventions included COS for IVF. MAIN OUTCOME MEASURES: VEGF-A levels in culture media were collected daily for 3 d from LGCs after incubation with variable doses of insulin, IGF-I, and IGF-II in the presence and absence of LH. RESULTS: In both study groups, exposure to LH alone did not alter VEGF-A levels. However, insulin or IGF increased VEGF-A levels within 1 d and appeared to synergize with LH at 3 d. VEGF-A production by non-PCOS LGCs was more sensitive to IGF exposure, whereas PCOS cells were more sensitive to insulin. Although an increase in DNA content (P < 0.05) was noted in cultures of PCOS cells, progesterone levels were lower compared with non-PCOS LGCs. CONCLUSION: Insulin and IGFs promote VEGF-A production in LGCs, but the response patterns are different when cells from PCOS and non-PCOS women are compared.

Linear regression model for predicting patient-specific total skeletal spongiosa volume for use in molecular radiotherapy dosimetry.

UNLABELLED: The toxicity of red bone marrow is widely considered to be a key factor in restricting the activity administered in molecular radiotherapy to suboptimal levels. The assessment of marrow toxicity requires an assessment of the dose absorbed by red bone marrow which, in many cases, requires knowledge of the total red bone marrow mass in a given patient. Previous studies demonstrated, however, that a close surrogate-spongiosa volume (combined tissues of trabecular bone and marrow)-can be used to accurately scale reference patient red marrow dose estimates and that these dose estimates are predictive of marrow toxicity. Consequently, a predictive model of the total skeletal spongiosa volume (TSSV) would be a clinically useful tool for improving patient specificity in skeletal dosimetry. METHODS: In this study, 10 male and 10 female cadavers were subjected to whole-body CT scans. Manual image segmentation was used to estimate the TSSV in all 13 active marrow-containing skeletal sites within the adult skeleton. The age, total body height, and 14 CT-based skeletal measurements were obtained for each cadaver. Multiple regression was used with the dependent variables to develop a model to predict the TSSV. RESULTS: Os coxae height and width were the 2 skeletal measurements that proved to be the most important parameters for prediction of the TSSV. The multiple R(2) value for the statistical model with these 2 parameters was 0.87. The analysis revealed that these 2 parameters predicted the estimated the TSSV to within approximately +/-10% for 15 of the 20 cadavers and to within approximately +/-20% for all 20 cadavers in this study. CONCLUSION: Although the utility of spongiosa volume in estimating patient-specific active marrow mass has been shown, estimation of the TSSV in active marrow-containing skeletal sites via patient-specific image segmentation is not a simple endeavor. However, the alternate approach demonstrated in this study is fairly simple to implement in a clinical setting, as the 2 input measurements (os coxae height and width) can be made with either pelvic CT scanning or skeletal radiography.

Circulating levels of total angiopoietin-2 and the soluble Tie-2 receptor in women during ovarian stimulation and early gestation.

Circulating levels of Ang-2 and sTie-2 receptor were detectable but invariant in women during COS cycles. During the postimplantation period, the rise in Ang-2 (but not sTie-2) levels probably reflects placental rather than luteal production.

Chord-based versus voxel-based methods of electron transport in the skeletal tissues.

Anatomic models needed for internal dose assessment have traditionally been developed using mathematical surface equations to define organ boundaries, shapes, and their positions within the body. Many researchers, however, are now advocating the use of tomographic models created from segmented patient computed tomography (CT) or magnetic resonance (MR) scans. In the skeleton, however, the tissue structures of the bone trabeculae, marrow cavities, and endosteal layer are exceedingly small and of complex shape, and thus do not lend themselves easily to either stylistic representations or in-vivo CT imaging. Historically, the problem of modeling the skeletal tissues has been addressed through the development of chord-based methods of radiation particle transport, as given by studies at the University of Leeds (Leeds, U.K.) using a 44-year male subject. We have proposed an alternative approach to skeletal dosimetry in which excised sections of marrow-intact cadaver spongiosa are imaged directly via microCT scanning. The cadaver selected for initial investigation of this technique was a 66-year male subject of nominal body mass index (22.7 kg m(-2)). The objectives of the present study were to compare chord-based versus voxel-based methods of skeletal dosimetry using data from the UF 66-year male subject. Good agreement between chord-based and voxel-based transport was noted for marrow irradiation by either bone surface or bone volume sources up to 500-1000 keV (depending upon the skeletal site). In contrast, chord-based models of electron transport yielded consistently lower values of the self-absorbed fraction to marrow tissues than seen under voxel-based transport at energies above 100 keV, a feature directly attributed to the inability of chord-based models to account for nonlinear electron trajectories. Significant differences were also noted in the dosimetry of the endosteal layer (for all source tissues), with chord-based transport predicting a higher fraction of energy deposition than given by voxel-based transport (average factor of about 1.6). The study supports future use of voxel-based skeletal models which (1) permit nonlinear electron trajectories across the skeletal tissues, (2) do not rely on mathematical algorithms for treating the endosteal tissue layer, and (3) do not implicitly assume independence of marrow and bone trajectories as is the case for chord-based skeletal models.

A comparison of skeletal chord-length distributions in the adult male.

In radiation protection, skeletal dose estimates are required for the tissues of the hematopoietically active bone marrow and the osteogenic cells of the trabecular and cortical endosteum. Similarly, skeletal radiation dose estimates are required in therapy nuclear medicine in order to develop dose-response functions for myelotoxicity where active bone marrow is generally the dose-limiting organ in cancer radioimmunotherapy. At the present time, skeletal dose models in both radiation protection and medical dosimetry are fundamentally reliant on a single set of chord-length distribution measurements performed at the University of Leeds in the late 1970's for a 44-y-old male subject. These distributions describe the relative frequency at which linear pathlengths are seen across both the marrow cavities and bone trabeculae in seven individual bone sites: vertebrae (cervical and lumbar), proximal femur (head and neck), ribs, cranium (parietal bone), and pelvis (iliac crest). In the present study, we present an alternative set of chord-length distribution data acquired within a total of 14 skeletal sites of a 66-y-old male subject. The University of Florida (UF) distributions are assembled via 3D image processing of microCT scans of physical sections of trabecular spongiosa at each skeletal site. In addition, a tri-linear interpolation Marching Cube algorithm is employed to smooth the digital surfaces of the bone trabeculae while chord-length measurements are performed. A review of mean chord lengths indicate that larger marrow cavities are noted on average in the UF individual for the cervical vertebrae (1,038 vs. 910 microm), lumbar vertebrae (1,479 vs. 1,233 microm), ilium (1,508 vs. 904 microm), and parietal bone (812 vs. 389 microm), while smaller marrow cavities are noted in the UF individual for the femoral head (1,043 microm vs. 1,157 microm), the femoral neck (1,454 microm vs. 1,655 microm), and the ribs (1,630 microm vs. 1,703 microm). The mean chord-lengths for the bone trabeculae show close agreement for both individuals in the ilium (approximately 240 microm) and cervical vertebrae (approximately 280 microm). Thicker trabeculae were seen on average in the UF individual for the femoral head (ratio of 1.50), femoral neck (ratio of 1.10), lumbar vertebrae (ratio of 1.29), and ribs (ratio of 1.14), while thinner trabeculae were seen on average in the UF individual for the parietal bone of the cranium (ratio of 0.92). In two bone sites, prominent discrepancies in chord distribution shape were noted between the Leeds 44-y-old male and the UF 66-y-old male: (1) the bone trabeculae in the ribs, and (2) the marrow cavities and bone trabeculae within the cranium.

Absorbed fractions for alpha-particles in tissues of trabecular bone: considerations of marrow cellularity within the ICRP reference male.

UNLABELLED: Alpha-particles are of current interest in radionuclide therapy due to their short range and high rates of energy transfer to target tissues. Published values of alpha-particle absorbed fraction phi in the skeletal tissues, as needed for patient-specific dosimetry under the MIRD schema, do not generally account for its variation with particle energy or skeletal site. Furthermore, variations in alpha-particle absorbed fraction with marrow cellularity have yet to be fully considered. METHODS: In this study, a 3-dimensional (3D) chord-based radiation transport model (or 3D-CBIST) is presented, which combines (a) chord-based techniques for tracking alpha-particles across bone trabeculae, endosteum, and marrow cavities and (b) a spatial model of the marrow tissues that explicitly considers the presence of marrow adipocytes. Chord-length distributions are taken from a 44-y male subject (ICRP [International Commission on Radiological Protection] Reference Male) and are identical to those used currently for clinical dose estimates for beta-particle emitters. RESULTS: Values of phi(active marrow<--active marrow) given by the 3D-CBIST model are shown to be considerably lower than phi = 1.0 assumed under the ICRP Publication 30 and 2003 Eckerman bone models. For example, values of absorbed fraction for the self-dose to active bone marrow in the ribs, cervical vertebra, and parietal bone are 0.81, 0.80, and 0.55 for 6-MeV alpha-particles and are 0.74, 0.72, and 0.43 for 9-MeV alpha-particles, where each is evaluated at ICRP reference cellularities in the 3D-CBIST model (72%, 72%, and 42%, respectively, at age 25 y). CONCLUSION: Improvements in patient-specific dosimetry of skeletal tissues require explicit consideration of not only changes in target mass with variable patient marrow cellularity (i.e., active marrow) but also corresponding changes in values of the absorbed fraction. The data given in this study provide a more-firm basis for application of the MIRD schema to patient-specific dosimetry for newly developing therapies using alpha-particle emitters.

Accounting for beta-particle energy loss to cortical bone via paired-image radiation transport (PIRT).

Current methods of skeletal dose assessment in both medical physics (radionuclide therapy) and health physics (dose reconstruction and risk assessment) rely heavily on a single set of bone and marrow cavity chord-length distributions in which particle energy deposition is tracked within an infinite extent of trabecular spongiosa, with no allowance for particle escape to cortical bone. In the present study, we introduce a paired-image radiation transport (PIRT) model which provides a more realistic three-dimensional (3D) geometry for particle transport in the skeletal site at both microscopic and macroscopic levels of its histology. Ex vivo CT scans were acquired of the pelvis, cranial cap, and individual ribs excised from a 66-year male cadaver (BMI of 22.7 kg m(-2)). For the three skeletal sites, regions of trabecular spongiosa and cortical bone were identified and segmented. Physical sections of interior spongiosa were taken and subjected to microCT imaging. Voxels within the resulting microCT images were then segmented and labeled as regions of bone trabeculae, endosteum, active marrow, and inactive marrow through application of image processing algorithms. The PIRT methodology was then implemented within the EGSNRC radiation transport code whereby electrons of various initial energies are simultaneously tracked within both the ex vivo CT macroimage and the CT microimage of the skeletal site. At initial electron energies greater than 50-200 keV, a divergence in absorbed fractions to active marrow are noted between PIRT model simulations and those estimated under existing techniques of infinite spongiosa transport. Calculations of radionuclide S values under both methodologies imply that current chord-based models may overestimate the absorbed dose to active bone marrow in these skeletal sites by 0% to 27% for low-energy beta emitters (33P, 169Er, and 177Lu), by approximately 4% to 49% for intermediate-energy beta emitters (153Sm, 186Re, and 89Sr), and by approximately 14% to 76% for high-energy beta emitters (32p, 188Re, and 90Y). The PIRT methodology allows for detailed modeling of the 3D macrostructure of individual marrow-containing bones within the skeleton thus permitting improved estimates of absorbed fractions and radionuclide S values for intermediate-to-high energy beta emitters.

A paired-image radiation transport model for skeletal dosimetry.

UNLABELLED: Toxicity of the hematopoietically active bone marrow continues to be a primary limitation in radionuclide therapies of cancer. Improved techniques for patient-specific skeletal dosimetry are thus crucial to the development of dose-response relationships needed to optimize these therapies (i.e., avoid both marrow toxicity and tumor underdosing). Current clinical methods of skeletal dose assessment rely heavily on a single set of bone and marrow cavity chord-length distributions in which particle energy deposition is tracked within an infinite extent of trabecular spongiosa, with no allowance for particle escape to cortical bone. In the present study, we introduce a paired-image radiation transport (PIRT) model that can provide a more realistic 3-dimensional geometry for particle transport of the skeletal site at both microscopic and macroscopic levels of its histology. METHODS: Ex vivo CT scans were acquired of the lumbar vertebra and right proximal femur excised from a 66-y male cadaver (body mass index, 22.7 kg m(-2)). For both skeletal sites, regions of trabecular spongiosa and cortical bone were identified and segmented. Physical sections of interior spongiosa were then taken and subjected to nuclear magnetic resonance (NMR) microscopy. Voxels within the resulting NMR microimages were segmented and labeled into regions of bone trabeculae, endosteum, active marrow, and inactive marrow. The PIRT methodology was then implemented within the EGSnrc radiation transport code, whereby electrons of various initial energies are simultaneously tracked within both the ex vivo CT macroimage and the NMR microimage of the skeletal site. RESULTS: At electron initial energies greater than 50-200 keV, a divergence in absorbed fractions to active marrow is noted between PIRT model simulations and those estimated under infinite spongiosa transport techniques. Calculations of radionuclide S values under both methodologies imply that current chord-based models used in clinical skeletal dosimetry can overestimate dose to active bone marrow in these 2 skeletal sites by approximately 4%-23% for low-energy beta-emitters ((33)P, (169)Er, and (177)Lu), by approximately 4%-25% for intermediate-energy beta-emitters ((153)Sm, (186)Re, and (89)Sr), and by approximately 11%-30% for high-energy beta-emitters ((32)P, (188)Re, and (90)Y). CONCLUSION: The PIRT methodology allows for detailed modeling of the 3D macrostructure of individual marrow-containing bones within the skeleton, thus permitting improved estimates of absorbed fractions and radionuclide S values for intermediate-to-high beta-emitters.

The diagnosis and reproductive outcome after surgical treatment of the complete septate uterus, duplicated cervix and vaginal septum.

OBJECTIVE: This study was undertaken to evaluate the diagnostic management and the reproductive outcome after surgical repair of a rare reproductive malformation. STUDY DESIGN: Sixteen women with a complete septate uterus, double cervix, and a longitudinal vaginal septum were referred for evaluation. Presenting complaints were chiefly pregnancy loss in parous women (n=9) and dyspareunia in nulligravid women (n=7). The combination of hysterosalpingography, ultrasonography, and/or magnetic resonance imaging was used to correctly identify the anomaly in 15 of the 16 cases. Both hysteroscopic (n=11) and transabdominal (n=5) surgical techniques were used to repair the uterine septum. RESULTS: In no case was the correct diagnosis made before referral; the uterus didelphys was the most common misdiagnosis. The preoperative pregnancy loss was 81%. Postoperatively, 12 women conceived for a total of 17 pregnancies; there were 14 term live births or ongoing pregnancies in the third trimester (82%), with a first trimester spontaneous abortion rate of 18%. In 9 women who conceived after hysteroscopic surgery, term live births occurred in 9 of 12 (75%) conceptions. A modified Tompkins metroplasty was performed in 5 women with subsequent term live births or ongoing third trimester pregnancies in 5 of 5 (100%) patients. CONCLUSION: The identification of a duplicated cervix and a vaginal septum is consistent with several uterine malformations, which leads to frequent misdiagnosis and errors in management. Significant pregnancy wastage, obstetric complications, and dyspareunia are common, and surgical treatment is therefore advisable. Making the best choice between hysteroscopic or transabdominal metroplasty depends on the anatomic features of the cervix and the uterine cavity, but optimal patient management requires familiarity with both techniques.

The role for preimplantation genetic diagnosis in balanced translocation carriers.

OBJECTIVE: Preimplantation genetic diagnosis is an established technique that provides an alternative to prenatal diagnosis for patients who are at risk of transmitting a serious genetic disorder to their offspring. Preimplantation genetic diagnosis has been used for couples who have been at risk for having offspring with single gene or X-linked disorders and for screening for common age-related aneuploidy and in couples who themselves carry balanced chromosomal rearrangements. The aim of this study was to summarize our experience using preimplantation genetic diagnosis after the identification of a parental balanced translocation, specifically as it relates to the number of embryos that are suitable for transfer after preimplantation genetic diagnosis for a known translocation and aneuploidy screening. STUDY DESIGN: This is a retrospective review of data from a single center that involved 6 couples that initiated the process of preimplantation genetic diagnosis for translocation and aneuploidy screening by fluorescent in situ hybridization. RESULTS: A total of 65 embryos were obtained, of which 56 embryos (86%) were suitable for fluorescent in situ hybridization analysis. After fluorescent in situ hybridization, 1 embryo was diagnosed as normal or balanced (1.7%). Forty-three embryos (76.8%) were unbalanced for the translocation; 8 embryos (14.3%) were aneuploid, and 4 embryos (7.1%) were uninformative. There were no clinical pregnancies. CONCLUSION: In our experience, there are very few embryos that are available for transfer from these patients after translocation and aneuploidy screening because of multiple unbalanced segregation products and a high rate of aneuploidy. Factors that contributed to this may be related to which parent carries the translocation, methods that were used for in vitro fertilization, and advanced maternal age. Although preimplantation genetic diagnosis for translocation carriers theoretically can enhance the pregnancy rate for a couple, there are limitations. This information should be shared with couples who are contemplating preimplantation genetic diagnosis for translocation, and the options of sperm or egg donor should be considered.

Pregnancy outcomes using donor sperm insemination after failed in vitro fertilization with intracytoplasmic sperm injection cycles in couples with complex infertility disorders.

OBJECTIVE: To evaluate alternatives for couples with severe male factor infertility who fail to conceive with IVF-intracytoplasmic sperm injection (ICSI). DESIGN: Outcomes of couples using artificial insemination with donor sperm (AID) after failed IVF-ICSI, assessing multiple risk factors affecting prognosis. SETTING: University infertility service. PATIENT(S): Nineteen patients with complex infertility disorders who failed IVF-ICSI and subsequently used AID (1 to 7 cycles). INTERVENTION(S): Artificial insemination with donor sperm was performed 36 hours after detection of an LH surge or hCG injection. MAIN OUTCOME MEASURE(S): Pregnancy outcomes were determined. RESULT(S): Seventeen pregnancies occurred in 16 women associated with AID for a pregnancy rate per cycle of 27.9% within a mean of 3.2 +/- 18 cycles. Live birth rate per cycle was 24.6%. CONCLUSION(S): A high pregnancy rate was achieved with AID in women who failed IVF-ICSI. Given the low cost and effectiveness of AID in this series, consideration of AID is a reasonable and effective option even in couples with poor prognosis who fail to conceive with IVF-ICSI.