Use of various gonadotropin and biosimilar formulations for in vitro fertilization cycles: results of a worldwide Web-based survey.

PURPOSE: The purpose of this study was to identify trends in gonadotropin therapy in patients undergoing in vitro fertilization (IVF) treatment worldwide. METHODS: Retrospective evaluation utilizing the results of a Web-based survey, IVF-Worldwide ( www.IVF-worldwide.com ) was performed. RESULTS: Three hundred fourteen centers performing a total of 218,300 annual IVF cycles were evaluated. Respondents representing 62.2% of cycles (n = 135,800) did not believe there was a difference between urinary and recombinant gonadotropins in terms of efficacy and live birth rate. Of the respondents, 67.3% (n = 146,800) reported no difference between recombinant and urinary formulations in terms of short-term safety and risk of ovarian hyperstimulation syndrome. In terms of long-term safety using human urinary gonadotropins, 50.6% (n = 110,400) of respondents believe there are potential long-term risks including prion disease. For 95.3% of units (n = 208,000), the clinician was the decision maker determining which specific gonadotropins are used for IVF. Of the units, 62.6% (n = 136,700) identified efficacy as the most important factor in deciding which gonadotropin to prescribe. While most (67.3%, n = 146,800) were aware of new biosimilar recombinant FSH products entering the market, 92% (n = 201,000) reported they would like more information. A fraction of respondents (25.6%, n = 55,900) reported having experience with these new products, and of these, 80.3% (n = 46,200) reported that they were similar in efficacy as previously used gonadotropins in a similar patient group. CONCLUSIONS: Respondents representing the majority of centers do not believe a difference exists between urinary and recombinant gonadotropins with respect to efficacy and live birth rates. While many are aware of new biosimilar recombinant FSH products entering the market, over 90% desire more information on these products.

Retained Products of Conception Associated with Intravasation of Hysterosalpingogram Contrast and Hysteroscopic Distention Media: A Case Report.

BACKGROUND: Hysteroscopic resection of retained products of conception has not been previously described to increase the risk for volume overload at the time of hysteroscopy. CASE: A 35-year-old woman with a history of recurrent pregnancy loss was evaluated by a hysterosalpingogram that identified retained products of conception with adjacent contrast intravasation. She underwent a hysteroscopic resection of the uterine septum and products of conception. During the 15 minute operating time she developed a fluid deficit of 2,300 cc of 3% sorbitol with resulting hyponatremia despite normal pressure and flow settings on the fluid management equipment. CONCLUSION: When a hysterosalpingogram demonstrates likely retained products of conception with an accompanying intravasation of contrast media, the provider should consider this finding a potential risk factor for excess intravasation of hysteroscopic distention media and take additional precautions to avoid volume overload.

Use of anti-mullerian hormone for testing ovarian reserve: a survey of 796 infertility clinics worldwide.

PURPOSE: The aim of this study is to assess how anti-mullerian hormone (AMH) is used worldwide to test ovarian reserve and guide in vitro fertilization (IVF) cycle management. METHODS: An internet-based survey was sent electronically to registered IVF providers within the IVF-Worldwide.com network. This survey consisted of nine questions which assessed the clinics' use of AMH. The questionnaire was completed online through the IVF-Worldwide.com website, and quality assurance tools were used to verify that only one survey was completed per clinical IVF center. Results are reported as the proportion of IVF cycles represented by a particular answer choice. RESULTS: Survey responses were completed from 796 globally distributed IVF clinics, representing 593,200 IVF cycles worldwide. Sixty percent of the respondent-IVF cycles reported to use AMH as a first line test, and 54 % reported it as the best test for evaluating ovarian reserve. Eighty-nine percent reported that AMH results were extremely relevant or relevant to clinical practice. However in contrast, for predicting live birth rate, 81 % reported age as the best predictor. CONCLUSIONS: AMH is currently considered a first line test for evaluating ovarian reserve and is considered relevant to clinical practice by the majority of IVF providers.

Measurement of antral follicle count in patients undergoing in vitro fertilization treatment: results of a worldwide web-based survey.

PURPOSE: The purpose of the present study was to identify trends in the therapeutic approaches used to measure antral follicle count (AFC) in patients undergoing in vitro fertilization (IVF) treatment worldwide. METHODS: A retrospective evaluation utilizing the results of a web-based survey, IVF-Worldwide ( www.IVF-Worldwide.com ), was performed. RESULTS: Responses from 796 centers representing 593,200 cycles were evaluated. The majority of respondents (71.2 %) considered antral follicle count as a mandatory part of their practice with most (69.0 %) measuring AFC in the follicular phase. Most respondents (89.7 %) reported that they would modify the IVF stimulation protocol based on the AFC. There was considerable variation regarding a limit for the number of antral follicles required to initiate an IVF cycle with 46.1 % designating three antral follicles as their limit, 39.9 % selecting either four or five follicles as their limit, and 14.0 % reporting a higher cutoff criteria. With respect to antral follicle size, 61.5 % included follicles ranging between 2 and 10 mm in the AFC. When asked to identify the best predictor of ovarian hyper-response during IVF cycles, AFC was selected most frequently (49.4 %), followed by anti-Mullerian hormone level (42.7 %). Age was selected as the best predictor of ongoing pregnancy rate in 81.7 % of respondents. CONCLUSIONS: While a large proportion of respondents utilized AFC as part of their daily practice and modified IVF protocol based on the measurement, the majority did not consider AFC as the best predictor of ongoing pregnancy rate.

Dexamethasone attenuates the embryotoxic effect of endometriotic peritoneal fluid in a murine model.

PURPOSE: The in vitro fertilization (IVF) pregnancy rate of women with advanced stage endometriosis is nearly half that of the general population, suggesting incomplete targeting of the pathophysiology underlying endometriosis-associated infertility. Compelling evidence highlights inflammation as the etiologic link between endometriosis and infertility and a potential target for adjunctive treatment. The objective of this study was to examine the effect of dexamethasone on murine embryos exposed to human endometriotic peritoneal fluid (PF) using the established murine embryo assay model. METHODS: PF was obtained from women with and without severe endometriosis. Murine embryos were harvested and randomly allocated to five groups of culture media conditions: (1) human tubal fluid (HTF), (2) HTF and 10 % PF from women without endometriosis, (3) HTF and 10 % PF from women with endometriosis (PF-E), (4) HTF with PF-E and 0.01 mcg/mL dexamethasone, and (5) HTF with PF-E and 0.1 mcg/mL dexamethasone. Embryos were cultured in standard conditions and evaluated for blastocyst development. RESULTS: A total of 266 mouse embryos were cultured. Baseline blastulation rates were 63.6 %. The addition of peritoneal fluid from women with endometriosis decreased the blastocyst development rate to 38.9 % (P = 0.008). The addition of 0.1 mcg/mL of dexamethasone to the culture media restored the blastulation rate to near baseline levels (61.2 %; P = 0.019). CONCLUSIONS: The results of our in vitro study demonstrate the capacity of dexamethasone to mitigate the deleterious impact of endometriotic PF on embryo development. If confirmed in vivo, dexamethasone may prove a useful adjunct for the treatment of endometriosis-associated infertility.

Blastocoel fluid from differentiated blastocysts harbors embryonic genomic material capable of a whole-genome deoxyribonucleic acid amplification and comprehensive chromosome microarray analysis.

OBJECTIVE: To obtain embryonic molecular karyotypes from genomic DNA (deoxyribonucleic acid) isolated from blastocoel fluid (BF) and to compare these karyotypes with the karyotypes from the remaining inner cell mass (ICM) and trophectoderm (TE) of the blastocyst. DESIGN: Prospective cohort study. SETTING: Academic center and preimplantation genetics laboratory. PATIENT(S): Ninety-six donated cryopreserved embryos. INTERVENTION(S): Embryo biopsy, BF aspiration, DNA analysis using a comparative genomic hybridization microarray (aCGH). MAIN OUTCOME MEASURE(S): The aCGH of a single blastomere, BF-DNA, and ICM-TE. RESULT(S): The BF-DNA samples resulted in a successful aCGH in 63% of cases. Discordance in karyotypes was found between the BF-DNA and the ICM-TE in 52% of cases. A total of 70% of aneusomic (mosaicism), cleavage-stage embryos differentiated into euploid blastocysts. Probabilities for diagnostic accuracy were calculated and demonstrated the following: sensitivity of 0.88 (95% confidence interval [CI]: 0.62-0.98); specificity of 0.55 (95% CI: 0.39-0.70); positive predictive value of 0.41 (95% CI: 0.25-0.60); negative predictive value of 0.92 (95% CI: 0.75-0.99). CONCLUSION(S): Genomic DNA from the BF can be amplified and characterized by comprehensive chromosome microarrays. The results demonstrated that aneusomic cleavage-stage embryos differentiated into euploid blastocysts, possibly using a mechanism that marginalizes aneuploid nuclei into the blastocoel cavity. In addition, owing to the high discordance between the karyotypes obtained from the BF-DNA and the ICM-TE, using BF-DNA for preimplantation genetic testing is not yet advised.

How to define, diagnose and treat poor responders? Responses from a worldwide survey of IVF clinics.

Poor responders represent a significant percentage of couples treated in IVF units (10-24%), but the standard definition of poor responders remains uncertain and consequently optimal treatment options remain subjective and not evidence-based. In an attempt to provide uniformity on the definition, diagnosis and treatment of poor responders, a worldwide survey was conducted asking IVF professionals a set of questions on this complex topic. The survey was posted on www.IVF-worldwide.com, the largest and most comprehensive IVF-focused website for physicians and embryologists. A total of 196 centres replied, forming a panel of IVF units with a median of 400 cycles per year. The present study shows that the definition of poor responders is still subjective, and many practices do not use evidence-based treatment for this category of patients. Our hope is that by leveraging the great potential of the internet, future studies may provide immediate large-scale sampling to standardize both poor responder definition and treatment options.

Spanish language content on reproductive endocrinology and infertility practice websites.

OBJECTIVE: To analyze the use of Spanish language translation on the websites of reproductive endocrinology and infertility (REI) practices in the context of evidence of underuse of infertility services by minority populations. DESIGN: Cross-sectional survey of websites from REI practices. SETTING: Not applicable. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Assessment of the relationship between having a Spanish-translated website and REI practice characteristics. Variables included concurrent use of social media, size of the practice, Spanish-speaking practitioner in the practice, being a private or a university-based practice, being in a mandated insurance state, and being in an area with different levels of percentage of Hispanic population, adjusted for annual income levels of the population. RESULT(S): Of the 376 REI practice websites analyzed, 101 (27%) offered at least some information in Spanish. We identified 97 Spanish-speaking practitioners at 71 REI practices. Having a Spanish-translated website was significantly associated with the practice's use of social media, having an international/out-of-town web page, and having a Spanish-speaking physician in the practice. The size of the practice, as measured in number of cycles reported per year, was not associated with having a translated website. In practices located in the top 60 metropolitan areas by Hispanic population, the odds of having a Spanish-translated website were only related to the percentage of Hispanic population after adjusting for state-mandated insurance and average annual income level of the Hispanic population. Sixty-six of the websites with Spanish-translated content had been automatically translated. An additional eight websites were partially translated automatically. CONCLUSION(S): REI practices in metropolitan areas with a higher percentage of Hispanics were more likely to reach out to this minority population by translating their website content into Spanish. These practices were also more likely to use social media. Future studies are needed to determine whether the availability of Spanish language content on REI websites is associated with increased use of reproductive services by this minority population.

Worldwide survey of IVF practices: trigger, retrieval and embryo transfer techniques.

PURPOSE: To identify common and varying practice patterns used by in vitro fertilization (IVF) providers from a broadly distributed, worldwide survey. Specific information regarding clinical IVF practices involving the oocyte maturation triggering, oocyte retrieval and embryo transfer was elicited. METHODS: This is an internet-based questionnaire study of IVF practices throughout the world. We used 26 multiple choice questions regarding common clinical practices. The data reported are weighted based on the number of IVF cycles performed at the specific IVF center, represented by a single respondent. RESULTS: Surveys were completed from 359 centers in 71 countries throughout the world. The most common practice patterns (defined as ≥75 % of IVF cycles) identified included: use of human chorionic gonadotropin (hCG) for trigger with an antagonist protocol, no routine patient monitoring from hCG trigger to oocyte retrieval, timing oocyte retrieval 34-37 h following oocyte maturing trigger, use of a single lumen retrieval needle, no routine tests following oocyte retrieval prior to patient discharge and use of ultrasound assistance with embryo transfer. CONCLUSIONS: This is the largest and most diversely represented survey of specific IVF practices addressing oocyte maturation triggers, oocyte retrieval and embryo transfers. Several uniform practice patterns were identified that can be correlated with evidence-based medicine; however, we identified multiple variable practice patterns which is likely the result of the absence of definitive evidence to guide IVF practitioners. The results of this survey allow IVF providers to compare their specific practice patterns with those of a global diverse population of IVF providers.

Two different microarray technologies for preimplantation genetic diagnosis and screening, due to reciprocal translocation imbalances, demonstrate equivalent euploidy and clinical pregnancy rates.

PURPOSE: To compare single nucleotide polymorphism (SNP) and comparative genomic hybridization (aCGH) microarray platforms to evaluate embryos for parental translocation imbalances and aneuploidy. METHODS: A retrospective review of preimplantation genetic diagnosis and screening (PGD/PGS) results of 498 embryos from 63 couples undergoing 75 in vitro fertilization cycles due to parental carriers of a reciprocal translocation. RESULTS: There was no significant difference between SNP and aCGH microarrays when comparing the prevalence of embryos that were euploid with no translocation imbalance, euploidy with a parental translocation imbalance or aneuploid with or without the parental chromosome imbalance. The clinical pregnancy rates were also equivalent for SNP (60 %) versus aCGH (65 %) microarrays. Of 498 diagnosed embryos, 45 % (226/498) were chromosomally normal without translocation errors or aneuploidy, 22 % (112/498) were euploid but had a parentally derived unbalanced chromosomal segregant, 8 % (42/498) harbored both a translocation imbalance and aneuploidy and 24 % (118/498) of embryos were genetically balanced for the parental reciprocal translocation but were aneuploid for other chromosomes. The overall clinical pregnancy rate per IVF cycle following SNP or aCGH microarray analysis was 61 % and was higher if the biopsy was done on blastocysts (65 %) versus cleavage stage embryos (59 %), although not statistically significant. CONCLUSIONS: SNP or aCGH microarray technologies demonstrate equivalent clinical findings that maximize the pregnancy potential in patients with known parental reciprocal chromosomal translocations.

Frequency of breast cancer, lung cancer, and tobacco use articles in women's magazines from 1987 to 2003.

BACKGROUND: The objective of this study was to compare the frequency of articles in women's magazines that address breast cancer, lung cancer, and tobacco use from 1987-2003 and to ascertain whether the annual number of articles reflected corresponding cancer mortality rates from breast cancer and lung cancer and the number of female smokers throughout this time period. METHODS: We reviewed 13 women's magazines published in the United States from 1987-2003 using the search terms breast cancer, lung cancer, smoking, and tobacco. We reviewed the abstracts or entire articles to determine relevance. RESULTS: A total of 1044 articles addressed breast cancer, lung cancer, or tobacco use: 681 articles related to breast cancer, 47 related to lung cancer, and 316 related to tobacco use. The greater number of breast cancer articles compared to lung cancer articles was statistically significant (P value < .0001). The greater number of breast cancer articles compared to lung cancer articles combined with tobacco use articles was also statistically significant (P = .0012). The annual number breast cancer articles compared to the breast cancer mortality rate demonstrated a negative relationship. The annual number of lung cancer articles compared to the lung cancer mortality rate demonstrated no relationship. The annual number of tobacco use articles compared to the annual number of female smokers demonstrated no relationship. CONCLUSIONS: Breast cancer was more frequently represented than lung cancer or tobacco use in women's magazines from 1987-2003 despite the increase in lung cancer mortality, a decrease in breast cancer mortality, and an insignificant change in the number of female smokers.