A multi-centre international study of salivary hormone oestradiol and progesterone measurements in ART monitoring.

RESEARCH QUESTION: Ovarian stimulation during IVF cycles involves close monitoring of oestradiol, progesterone and ultrasound measurements of follicle growth. In contrast to blood draws, sampling saliva is less invasive. Here, a blind validation is presented of a novel saliva-based oestradiol and progesterone assay carried out in samples collected in independent IVF clinics. DESIGN: Concurrent serum and saliva samples were collected from 324 patients at six large independent IVF laboratories. Saliva samples were frozen and run blinded. A further 18 patients had samples collected more frequently around the time of HCG trigger. Saliva samples were analysed using an immunoassay developed with Salimetrics LLC. RESULTS: In total, 652 pairs of saliva and serum oestradiol were evaluated, with correlation coefficients ranging from 0.68 to 0.91. In the European clinics, a further 237 of saliva and serum progesterone samples were evaluated; however, the correlations were generally poorer, ranging from -0.02 to 0.22. In the patients collected more frequently, five out of 18 patients (27.8%) showed an immediate decrease in oestradiol after trigger. When progesterone samples were assessed after trigger, eight out of 18 (44.4%) showed a continued rise. CONCLUSIONS: Salivary oestradiol hormone testing correlates well to serum-based assessment, whereas progesterone values, around the time of trigger, are not consistent from patient to patient.

Types and frequency of non-conformances in an IVF laboratory.

STUDY QUESTION: How many non-conformances occur in an ART laboratory and how often do they occur? SUMMARY ANSWER: The limited data to date demonstrate that IVF laboratories have a very low non-conformance rate compared with reported non-conformances in other medical laboratories, especially when one considers the high-complexity of procedures performed. WHAT IS KNOWN ALREADY: ART involves a series of very complex patient and laboratory procedures. Although it is assumed that strict measures control ART laboratories, there is very little published data on non-conformances. STUDY DESIGN, SIZE, DURATION: In accordance with the ISO 9001:2008 standard, Boston IVF has created an electronic database to record non-conformances in the IVF laboratory. We reviewed the non-conformances reported between March 2003 and December 2015. The non-conformances were categorized into four grades largely based upon their impact on the outcome or continuation of an IVF treatment cycle: None/Minimal (not measurably decreasing the likelihood of success), Moderate (a negative impact but not loss of a cycle), Significant (loss of a cycle or majority of gametes or embryos) and Major (infrequent errors that have an extreme impact on a patient or patients such as a confirmed pregnancy or birth involving misidentification of sperm, egg or embryo, or an extreme equipment or documentation failure that affects numerous patients). The category of problem or error associated with the Non-conformance Report was also noted. PARTICIPANTS/MATERIALS, SETTING, METHOD: Retrospective analysis of an electronic database registering non-conformances at a large IVF laboratory. MAIN RESULTS AND THE ROLE OF CHANCE: During the study period, a total of 36 654 IVF treatment cycles (fresh and frozen embryo transfer cycles) were conducted which involved a total of 181 899 individual laboratory procedures encompassing egg retrievals, sperm preparations, inseminations, embryo transfers, etc. When combining both moderate and significant non-conformances, 99.96% of procedures and 99.77% of cycles proceeded with no non-conformances. No Major grade non-conformances were reported. LIMITATIONS, REASONS FOR CAUTION: A comparison of non-conformances between IVF clinics is difficult because of different classifications. WIDER IMPLICATIONS OF THE FINDINGS: Errors are inevitable and it is incumbent on all IVF centers to be honest and transparent, both within the organization and with patients when errors occur. Robust systems for identifying, documenting, analyzing and implementing improvements should be established and maintained. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. The authors have no conflicts of interest.

Ovarian stimulation protocols for IVF: is more better than less?

Conventional ovarian stimulation protocols for IVF are designed to achieve maximum oocyte yields. Conventional protocols, however, are associated with patient discomfort, increased risk of ovarian hyperstimulation syndrome and higher costs. In recent years, mild stimulation protocols have risen in popularity. These protocols typically use lower doses (≤150 IU/day), shorter duration of exogenous gonadotrophins, or both, compared with conventional protocols, with the goal of limiting the number of retrieved oocytes to less than eight. The pregnancy rate per cycle (fresh embryo transfer only) is lower with mild stimulation compared with conventional stimulation; however, the cumulative pregnancy rate seems to be comparable between the approaches. Reports are conflicting on the effects of mild versus conventional stimulation on embryo quality. This article expands on a live debate held at the American Society for Reproductive Medicine 2015 Annual Meeting to compare the advantages and disadvantages of the 'more is better' (conventional protocol) versus 'less is best' (mild protocol) approaches to ovarian stimulation. Both protocols are associated with benefits and challenges, and physicians must consider the needs of the individual patient when determining the best treatment options. Further prospective studies comparing a variety of outcomes with conventional and mild stimulation are needed.

Pharmacokinetics and follicular dynamics of corifollitropin alfa versus recombinant FSH during ovarian stimulation for IVF.

A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH (rFSH) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection. This double-blind randomized controlled trial assessed the pharmacokinetics and pharmacodynamics of 150 µg corifollitropin alfa versus daily 200 IU rFSH in 1509 patients. Comparative analyses were performed on serum concentrations of FSH immunoreactivity (pharmacokinetics), and the number and size of growing follicles, and inhibin B and oestradiol concentrations as biomarkers of ovarian response (pharmacodynamics). The rate of follicular development was similar in both treatment groups. By stimulation day 8, 33% of patients treated with corifollitropin alfa reached the criterion for human chorionic gonadotrophin (HCG) injection. The number of follicles ≥11 mm was slightly higher after corifollitropin alfa compared with daily rFSH at stimulation day 8 (difference, 1.2; 95% confidence interval (Cl) 0.5-1.8; P < 0.01) and on the day of HCG injection (difference, 2.1; 95% Cl 1.4-2.8; P < 0.01). The rise of inhibin B and oestradiol concentrations was similar in both treatment groups. Although the pharmacokinetics of corifollitropin alfa and rFSH are quite different their pharmacodynamic profiles at the dosages used are similar.

Validation study of the Access antimüllerian hormone assay for the prediction of poor ovarian response to controlled ovarian stimulation.

OBJECTIVE: To evaluate the diagnostic performance of the antimüllerian hormone (AMH) level determined using the Access AMH assay for predicting poor ovarian response (POR) defined as ≤4 oocytes retrieved, including the validation of the predefined AMH cutoff of 0.93 ng/mL in both serum and plasma. DESIGN: Prospective cohort study. SETTING: Fifteen private and academic fertility centers (14 in the United States and 1 in Canada). PATIENT(S): Women aged 21-45 years planning controlled ovarian stimulation for in vitro fertilization. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, categorized as POR and normal-to-high ovarian response (non-POR). The correlation of AMH level and antral follicle count. RESULT(S): Data were available for 472 participants who completed the study (74 with POR and 398 non-POR). The mean AMH serum level among those with POR was 0.99 ng/mL (median 0.76 ng/mL) compared with 2.83 ng/mL (median 2.36 ng/mL) among the normal-to-high responders. For confirmation of the 0.93 ng/mL AMH level cutoff as a predictor of POR, a receiver operating characteristic analysis gave an area under the curve of 0.852, with corresponding sensitivity and specificity of 63.5% and 89.2%, respectively. The associated positive predictive value was 52.2% and the negative predictive value was 92.9%. The AMH plasma values demonstrated a strong correlation with AMH serum values with an r value = 0.9980. The previously established AMH cutoff of 1.77 ng/mL for antral follicle count >15 resulted in a sensitivity of 83.8% (95% confidence interval [CI] 77.7-88.5) and a specificity of 59.9% (95% CI 54.2-65.4). CONCLUSION(S): This study validated the previously established AMH cut-point for the prediction of POR. Because this cut-point may vary depending on the assay used, the specific AMH assay should be reported in the literature whenever possible.

Pharmacokinetics and follicular dynamics of corifollitropin alfa versus recombinant FSH during ovarian stimulation for IVF.

A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH (rFSH) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection. This double-blind randomized controlled trial assessed the pharmacokinetics and pharmacodynamics of 150µg corifollitropin alfa versus daily 200IU rFSH in 1509 patients. Comparative analyses were performed on serum concentrations of FSH immunoreactivity (pharmacokinetics), and the number and size of growing follicles, and inhibin B and oestradiol concentrations as biomarkers of ovarian response (pharmacodynamics). The rate of follicular development was similar in both treatment groups. By stimulation day 8, 33% of patients treated with corifollitropin alfa reached the criterion for human chorionic gonadotrophin (HCG) injection. The number of follicles ⩾11mm was slightly higher after corifollitropin alfa compared with daily rFSH at stimulation day 8 (difference, 1.2; 95% confidence interval (CI) 0.5-1.8; P<0.01) and on the day of HCG injection (difference, 2.1; 95% CI 1.4-2.8; P<0.01). The rise of inhibin B and oestradiol concentrations was similar in both treatment groups. Although the pharmacokinetics of corifollitropin alfa and rFSH are quite different their pharmacodynamic profiles at the dosages used are similar. A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH (rFSH) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection. The objective of this study was to compare the pharmacokinetics and pharmacodynamics of corifollitropin alfa versus daily rFSH. A total of 1509 patients were randomized in a double-blind, controlled trial to either a single injection of 150µg corifollitropin alfa or to daily injections of 200IU rFSH for the first 7 days of ovarian stimulation. Serum levels of FSH immunoreactivity were analysed (pharmacokinetic analysis), together with the number and size of growing follicles and serum inhibin B and oestradiol concentrations as biomarkers of the ovarian response (pharmacodynamic analysis). Serum FSH immunoreactivity levels were higher up to stimulation day 5 for corifollitropin alfa compared with the daily rFSH regimen but were similar from day 8 onwards, when patients started rFSH if the criteria for human chorionic gonadotrophin were not yet reached. Corifollitropin alfa treatment resulted in a similar growth rate of follicles though a slightly higher number of follicles were recruited compared with daily rFSH. It is concluded that the pharmacokinetics of corifollitropin alfa and rFSH are quite different but their induced pharmacodynamic effects at the dosages used are similar.

Economic evaluation of highly purified human menotropin or recombinant follicle-stimulating hormone for controlled ovarian stimulation in high-responder patients: analysis of the Menopur in Gonadotropin-releasing Hormone Antagonist Single Embryo Transfer-High Responder (MEGASET-HR) trial.

OBJECTIVE: To determine the cost of achieving a live birth after first transfer using highly purified human menotropin (HP-hMG) or recombinant follicle-stimulating hormone (FSH) for controlled ovarian stimulation in predicted high-responder patients in the Menopur in Gonadotropin-releasing hormone Antagonist Single Embryo Transfer-High Responder (MEGASET-HR) trial. DESIGN: Cost minimization analysis of trial results. SETTING: Thirty-one fertility centers. PATIENTS: Six hundred and nineteen women with serum antimüllerian hormone ≥5 ng/mL. INTERVENTIONS: Controlled ovarian stimulation with HP-hMG or recombinant FSH in a gonadotropin-releasing hormone (GnRH) antagonist assisted reproduction cycle where fresh transfer of a single blastocyst was performed unless ovarian response was excessive whereupon all embryos were cryopreserved and patients could undergo subsequent frozen blastocyst transfer within 6 months of randomization. MAIN OUTCOME MEASURES: Mean cost of achieving live birth after first transfer (fresh or frozen). RESULTS: First-transfer efficacy, defined as live birth after first fresh or frozen transfer, was 54.5% for HP-hMG and 48.0% for recombinant FSH (difference 6.5%). Average cost to achieve a live birth after first transfer (fresh or frozen) was lower with HP-hMG compared with recombinant FSH. For fresh transfers, the cost was lower with HP-hMG compared with recombinant FSH. The average cost to achieve a live birth after first frozen transfer was also lower in patients treated with HP-hMG compared with recombinant FSH. CONCLUSIONS: Treatment of predicted high-responders with HP-hMG was associated with lower cost to achieve a live birth after first transfer compared with recombinant FSH. CLINICAL TRIAL REGISTRATION NUMBER: NCT02554279.

Breast abscess in a competitive high school swimmer: a case of toxic shock syndrome.

Toxic shock syndrome (TSS) is a severe, acute, toxin-mediated disease process characterized by fever, diffuse erythroderma, hypotension, multisystem organ dysfunction and desquamation of skin. TSS represents the most severe form of disease caused by exotoxin-producing strains of Streptococcus pyogenes and Staphylococcus aureus. Menstrual and non-menstrual TSS become significant causes of morbidity and mortality. As a result of public awareness and various campaigns, the majority of TSS cases tend to be non-menstrual related. The clinical course is fulminant and can result in abrupt decompensation and death. Management within the emergency department (ED) includes removal of the potential foreign body, fluid resuscitation, appropriate antibiotics, potential vasopressor support and possible surgical intervention. We present the unique case of a 16-year-old female competitive swimmer who presented to the ED twice, demonstrating the fulminant course of TSS. She initially presented with non-specific symptoms with an unremarkable evaluation. She returned within hours of discharge with an abrupt onset of diffuse macular erythroderma, placed on norepinephrine and was diagnosed with TSS secondary to a breast abscess.

Assessment of the biopotency of follitropin alfa and lutropin alfa combined in one injection: a comparative trial in Sprague-Dawley rats.

BACKGROUND: The current study was designed to determine if follitropin alfa (recombinant human follicle-stimulating hormone; r-hFSH) and lutropin alfa (recombinant human luteinizing hormone; r-hLH) biopotencies were unchanged by reconstituting in sterile water for injection and mixing prior to injection. METHODS: The biopotencies of r-hFSH and r-hLH were determined following injection of female Sprague-Dawley rats with a mixture of follitropin alfa revised formulation female (RFF) and lutropin alfa (1:1, r-hFSH:r-hLH). Biopotencies of follitropin alfa RFF and lutropin alfa were measured using ovarian weight and ascorbic acid depletion assays, respectively, and compared with a reference standard. Stock mixtures of follitropin alfa RFF and lutropin alfa (1:1) were prepared within 1 h prior to each respective assay's injection and stored at 6 +/- 2 degrees C. Separate low dose (follitropin alfa RFF 1.5 IU/rat, lutropin alfa 2 IU/rat) and high dose (follitropin alfa RFF 3 IU/rat, lutropin alfa 8 IU/rat) treatments were prepared from stock mixtures or individual solutions by diluting with 0.22% bovine serum albumin saline solution and injected within 1 h of preparation. The main outcome measures were ovarian weight and ovarian ascorbic acid depletion. RESULTS: FSH bioactivities were similar (p > 0.10) between the individual follitropin alfa RFF test solution (84.2 IU) and follitropin alfa RFF/lutropin alfa (87.6 IU) mixtures prepared within 1 h of injection and stored at 6 +/- 2 degrees C. LH bioactivities were similar (p > 0.10) between lutropin alfa (94.7 IU) test solution and lutropin alfa/follitropin alfa RFF (85.3 IU) mixtures prepared within 1 h of injection and stored at 6 +/- 2 degrees C for not more than 1 h prior to injection. CONCLUSION: Mixing follitropin alfa RFF and lutropin alfa did not alter the bioactivity of either FSH or LH.

Multicenter evaluation of the Access AMH antimüllerian hormone assay for the prediction of antral follicle count and poor ovarian response to controlled ovarian stimulation.

OBJECTIVE: To evaluate a new fully automated antimüllerian hormone (AMH) assay for prediction of poor ovarian response (POR) to ovarian stimulation defined as four or fewer oocytes retrieved. DESIGN: Prospective cohort study. SETTING: Thirteen private and academic fertility centers in the United States. PATIENTS(S): A total of 178 women undergoing their first in vitro fertilization (IVF) cycle eligible for the study were consented and enrolled, with data available from 160 women for prediction of POR and 164 women for AMH correlation with antral follicle count (AFC). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cutoff point for AMH that predicts POR. Correlation of AMH with AFC, and cutoff point for AMH that correlates with antral follicle count >15. RESULT(S): The mean AMH among the poor responders was 0.74 ng/mL, compared with 3.20 ng/mL for normal to high responders. The AMH cutoff at 90% specificity for predicting POR with the use of the receiver operating characteristic (ROC) curve was 0.93 ng/mL, with an associated sensitivity of 74.1%. For prediction of POR, ROC analysis showed that AMH (area under the ROC curve [AUC] = 0.929) was significantly better than FSH (AUC = 0.615; P<.0001). AMH was positively correlated with AFC (Spearman rho = 0.756). The AMH at 90% sensitivity for AFC >15 was 1.75, with specificity of 59.1%. CONCLUSION(S): A fully automated AMH assay can be a useful biomarker for predicting POR in IVF cycles. Because AMH cutoff points vary depending on the assay used, future studies should continue to calibrate test results to clinically important outcomes.

How many oocytes are optimal to achieve multiple live births with one stimulation cycle? The one-and-done approach.

OBJECTIVE: To study how many infertility patients would complete an average-sized family (achieve ≥2 live births) after a single, complete in vitro fertilization (IVF) cycle. DESIGN: A retrospective cohort study. SETTING: University-affiliated private infertility practice. PATIENT(S): Women undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The outcome of 1 or ≥2 live births after a single retrieval cycle, followed by use of all embryos in subsequent frozen cycles in relation to oocyte number. RESULT(S): The pregnancy rate was statistically significantly higher when ≥15 oocytes were retrieved (289 of 699, 41.3%) than <15 oocytes (518 of 1,419, 36.5%). When investigating the outcome of ≥2 live births and assuming that all remaining frozen embryos were used, we found that 498 of 2,226 (22.4%) patients would achieve ≥2 live births. We performed multivariate analysis, and the area under the receiver operating characteristic curve for the model was 0.802. When controlling for multiple factors we found that as the number of oocytes retrieved increased, the chance of at least two live births increased, with odds ratio 1.08 (8% live birth increase per additional oocyte). CONCLUSION(S): We demonstrate that one fresh cycle with high oocyte yield is an optimal way to plan IVF treatment. With modern cryopreservation methods, the concept of "one-and-done" could safely achieve ≥2 live births with just one stimulation cycle in almost a quarter of our patients.

In vitro fertilization outcomes: why doesn't anyone get it?

It is not only patients who frequently do not understand the implications of multiple pregnancies and IVF outcomes in general. Physicians, insurers, and governments must share the responsibility for failing to properly address both overall and multiple pregnancy rates after IVF.

Initiation of the gonadotropin-releasing hormone antagonist ganirelix for in vitro fertilization cycles in which the lead follicle is >14 mm.

The initiation of GnRH antagonists when the lead follicle is >14 mm does not adversely affect IVF success rates and leads to a shortened duration of GnRH antagonist administration.

A mesothelial cyst of the round ligament presenting as an inguinal hernia after gonadotropin stimulation for in vitro fertilization.

OBJECTIVE: To report the case of a round ligament cyst which, as the result of gonadotropin stimulation for IVF, simulated an incarcerated inguinal hernia. DESIGN: Case report. SETTING: A private infertility center and a university hospital. PATIENT(S): A 31-year-old woman who developed left lower quadrant pain after gonadotropin stimulation for IUI and a tender left inguinal mass after increasing ovarian stimulation for IVF/intracytoplasmic sperm injection. INTERVENTION(S): Surgical excision of a mesothelial cyst of the left round ligament and exploration of the left inguinal canal. MAIN OUTCOME MEASURE(S): Successful surgical excision of left inguinal mass. RESULT(S): Resolution of symptoms. CONCLUSION(S): Mesothelial cysts of the round ligament should be included in the differential diagnosis of inguinal masses in women. Gonadotropin stimulation might cause previously unrecognized cysts to simulate an incarcerated inguinal hernia, necessitating surgical repair.

Variations in individual physician success rates within an in vitro fertilization program might be due to patient demographics.

OBJECTIVE: To determine whether there are variations in individual physician success rates in an IVF program, even with uniform laboratory and treatment protocols. DESIGN: Retrospective analysis. SETTING: Boston IVF, a private practice. PATIENT(S): Patients <38 and 38-40 years of age who underwent non-donor egg, fresh embryo transfer (ET). INTERVENTION(S): Retrospective analysis of IVF success rates for Boston IVF for the year 1999, as reported to the Society of Assisted Reproductive Technology. MAIN OUTCOME MEASURE(S): Each individual physician's clinical pregnancy and live birth rates for patients aged <38 and 38-40 years for the year 1999. Pregnancy rates were also obtained for an "ideal patient group." RESULT(S): Among 13 physicians, the clinical pregnancy rate in the <38-year age group ranged from 20.5% to 35.1% and the live birth rates from 17.8% to 31.1%. For the 38-40-year age group, the clinical pregnancy rate ranged from 10.6% to 29.8% and live birth rates from 7.0% to 25.5%. There was no statistical difference in the clinical pregnancy rate for the ideal patient group. CONCLUSION(S): In the ideal patient group, in which patient demographics are uniform, there are no statistical differences in individual physician performance within the same IVF program. Variation exists in the success rates between the physicians in the <38- and 38-40-year age groups. Possibly this is owing to patient demographics.

When is clomiphene or gonadotropin intrauterine insemination futile? Results of the Fast Track and Standard Treatment Trial and the Forty and Over Treatment Trial, two prospective randomized controlled trials.

OBJECTIVE: To determine whether day 3 FSH and E2 levels at the upper limits of normal affect live-birth rates and treatment trajectory in a conventional versus "fast track" treatment program for IVF. DESIGN: Secondary analysis of two randomized controlled trials, FASTT and FORT-T. SETTING: Not applicable. PATIENT(S): Infertile women ages 21-42 years randomized to conventional or accelerated treatment with controlled ovarian hyperstimulation (COH)-IUI and/or IVF (n=603 patients contributing 2,717 total cycles). INTERVENTION(S): Patients were stratified according to basal FSH and E2: FSH<10 mIU/mL and E2<40 pg/mL (group 1A), FSH<10 mIU/mL and E2≥40 pg/mL (group 1B), FSH, 10-15 mIU/mL and E2<40 pg/mL (group 2A), and FSH, 10-15 mIU/mL and E2≥40 pg/mL (group 2B). MAIN OUTCOME MEASURE(S): Number of cancelled cycles, disenrollment for poor response, and cumulative live-birth rates per couple. RESULT(S): Women in groups 2A and 2B were more likely to have cancelled cycles and be disenrolled for poor response. While no live births occurred in group 2B during COH-IUI (0/19 couples, 0/58 cycles), IVF still afforded these patients a reasonable chance of success (6/18 couples, 6/40 cycles, 33.3% live-birth rate per couple). The specificity and positive predictive value of basal FSH of 10-15 mIU/mL and E2≥40 pg/mL for no live birth during COH-IUI treatment were both 100%. CONCLUSION(S): Women who initiated infertility treatment with FSH of 10-15 mIU/mL and E2≥40 pg/mL on day 3 testing were unlikely to achieve live birth after COH-IUI treatment.

A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T).

OBJECTIVE: To determine the optimal infertility therapy for women at the end of their reproductive potential. DESIGN: Randomized clinical trial. SETTING: Academic medical centers and private infertility center in a state with mandated insurance coverage. PATIENT(S): Couples with ≥ 6 months of unexplained infertility; female partner aged 38-42 years. INTERVENTION(S): Randomized to treatment with two cycles of clomiphene citrate (CC) and intrauterine insemination (IUI), follicle stimulating hormone (FSH)/IUI, or immediate IVF, followed by IVF if not pregnant. MAIN OUTCOME MEASURE(S): Proportion with a clinically recognized pregnancy, number of treatment cycles, and time to conception after two treatment cycles and at the end of treatment. RESULT(S): We randomized 154 couples to receive CC/IUI (N = 51), FSH/IUI (N = 52), or immediate IVF (N = 51); 140 (90.9%) couples initiated treatment. The cumulative clinical pregnancy rates per couple after the first two cycles of CC/IUI, FSH/IUI, or immediate IVF were 21.6%, 17.3%, and 49.0%, respectively. After all treatments, 110 (71.4%) of 154 couples had conceived a clinically recognized pregnancy, and 46.1% had delivered at least one live-born baby; 84.2% of all live-born infants resulting from treatment were achieved via IVF. There were 36% fewer treatment cycles in the IVF arm compared with either COH/IUI arm, and the couples conceived a pregnancy leading to a live birth after fewer treatment cycles. CONCLUSION(S): A randomized controlled trial in older women with unexplained infertility to compare treatment initiated with two cycles of controlled ovarian hyperstimulation/IUI versus immediate IVF demonstrated superior pregnancy rates with fewer treatment cycles in the immediate IVF group. CLINICAL TRIAL REGISTRATION NUMBER: NCT00246506.

Experience with ISO quality control in assisted reproductive technology.

Assisted reproductive technology (ART) programs are complex organizations requiring the integration of multiple disciplines. ISO 9001:2008 is a quality management system that is readily adaptable to an ART program. The value that ISO brings to the entire organization includes control of documents, clear delineation of responsibilities of staff members, documentation of the numerous processes and procedures, improvement in tracking and reducing errors, and overall better control of systems. A quality ART program sets quality objectives and monitors their progress. ISO provides a sense of transparency within the organization and clearer understanding of how service is provided to patients. Most importantly, ISO provides the framework to allow for continual improvement.

Impact of a group mind/body intervention on pregnancy rates in IVF patients.

OBJECTIVE: To determine if women who were randomized to a mind/body program before starting their first IVF cycle would have higher pregnancy rates than control subjects. DESIGN: Randomized, controlled, prospective study. SETTING: Private academically affiliated infertility center. PATIENT(S): A total of 143 women aged≤40 years who were about to begin their first IVF cycle. INTERVENTION(S): Subjects were randomized to a ten-session mind/body program (MB) or a control group and followed for two IVF cycles. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate. RESULT(S): Only 9% of the MB participants had attended at least one-half of their sessions at cycle 1 start. Pregnancy rates for cycle 1 were 43% for all subjects; 76% of the MB subjects had attended at least one-half of their sessions at cycle 2 start. Pregnancy rates for cycle 2 were 52% for MB and 20% for control. CONCLUSION(S): MB participation was associated with increased pregnancy rates for cycle 2, prior to which most subjects had attended at least half of their sessions.

A prospective investigation into the reasons why insured United States patients drop out of in vitro fertilization treatment.

OBJECTIVE: To determine the primary reason why insured patients drop out of IVF treatment in the United States and to identify methods to decrease such behavior. DESIGN: Prospective patient survey. SETTING: Private infertility clinic. PATIENT(S): Women under the age of 40 years, who had insurance coverage for at least three IVF cycles, who did not conceive and who did not return to the clinic for a third treatment cycle. INTERVENTION(S): One hundred thirty-two eligible patients received a study packet of questionnaires in the mail. MAIN OUTCOME MEASURE(S): Subject responses to questionnaire. RESULT(S): Forty-seven subjects returned the questionnaire. The most common reason for terminating treatment was stress (39%). Subjects reported that the two main causes of stress were the toll that infertility took on the couples' relationship and being too anxious or depressed to continue. The top-rated suggestions for patient support were written information on how to deal with psychological stress and easy and immediate access to a psychologist or social worker. CONCLUSION(S): Patients undergoing IVF in the United States report similar reasons for terminating treatment as patients in Europe and Australia. However, this is the first study to gather patient suggestions for treating the problem.