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.

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.

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.

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.

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.

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.

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.

Advances in polycystic ovary syndrome treatment: metformin and ovarian diathermy.

Polycystic ovary syndrome (PCOS) affects approximately 6% of women in their reproductive years. The symptoms of the syndrome are chronic anovulation and androgen excess. Infertility due to ovulatory dysfunction is a common problem for women with PCOS. Metformin, an antihyperglycemic agent, can correct the metabolic dysfunction that occurs with PCOS, and also stimulate folliculogenesis. The drug is effective alone and in combination with clomiphene citrate. An alternative option, ovarian diathermy, also promotes ovulation through changes in the intraovarian hormonal environment. Both techniques provide promising and effective alternatives for women with PCOS who do not respond to traditional oral ovulation induction agents.

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.

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