Boston IVF

Embryonic stem cells have the unique ability to form all adult cell types. Harnessing this potential may provide a source of cells to replace those that are lost or impaired as a result of disease. Moreover, the derivation of human embryonic stem cells opens a unique window into the study of early human development. At present, approximately 15 human embryonic stem-cell lines are publicly available, and they vary considerably in their usefulness for research and the extent of their characterization (see http://stemcells.nih.gov/registry/index.asp). To promote further research with human embryonic stem cells, we sought to derive and characterize more fully cell lines that meet strict criteria for ease of manipulation, including enzymatic passage with trypsin, streamlined freezing and thawing procedures, well-defined culture mediums, and straightforward methods for in vitro differentiation. We report the derivation and characterization of 17 additional human embryonic stem cell lines.

The relationship between stress and infertility has been debated for years. Women with infertility report elevated levels of anxiety and depression, so it is clear that infertility causes stress. What is less clear, however, is whether or not stress causes infertility. The impact of distress on treatment outcome is difficult to investigate for a number of factors, including inaccurate self-report measures and feelings of increased optimism at treatment onset. However, the most recent research has documented the efficacy of psychological interventions in lowering psychological distress as well as being associated with significant increases in pregnancy rates. A cognitive-behavioral group approach may be the most efficient way to achieve both goals. Given the distress levels reported by many infertile women, it is vital to expand the availability of these programs.

BACKGROUND: Outcomes of in vitro fertilization (IVF) treatment are traditionally reported as pregnancies per IVF cycle. However, a couple's primary concern is the chance of a live birth over an entire treatment course. METHODS: We estimated cumulative live-birth rates among patients undergoing their first fresh-embryo, nondonor IVF cycle between 2000 and 2005 at one large center. Couples were followed until either discontinuation of treatment or delivery of a live-born infant. Analyses were stratified according to maternal age and performed with the use of both optimistic and conservative methods. Optimistic methods assumed that patients who did not return for subsequent IVF cycles would have the same chance of a pregnancy resulting in a live birth as patients who continued treatment; conservative methods assumed no live births among patients who did not return. RESULTS: Among 6164 patients undergoing 14,248 cycles, the cumulative live-birth rate after 6 cycles was 72% (95% confidence interval [CI], 70 to 74) with the optimistic analysis and 51% (95% CI, 49 to 52) with the conservative analysis. Among patients who were younger than 35 years of age, the corresponding rates after six cycles were 86% (95% CI, 83 to 88) and 65% (95% CI, 64 to 67). Among patients who were 40 years of age or older, the corresponding rates were 42% (95% CI, 37 to 47) and 23% (95% CI, 21 to 25). The cumulative live-birth rate decreased with increasing age, and the age-stratified curves (< 35 vs. > or = 40 years) were significantly different from one another (P<0.001). CONCLUSIONS: Our results indicate that IVF may largely overcome infertility in younger women, but it does not reverse the age-dependent decline in fertility.

a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

BACKGROUND: Preimplantation genetic screening (PGS) has been used in an attempt to determine embryonic aneuploidy. Techniques that use new molecular methods to determine the karyotype of an embryo are expanding the scope of PGS. METHODS: We introduce a new method for PGS, termed 'parental support', which leverages microarray measurements from parental DNA to 'clean' single-cell microarray measurements on embryonic cells and explicitly computes confidence in each copy number call. The method distinguishes mitotic and meiotic copy errors and determines parental source of aneuploidy. RESULTS: Validation with 459 single cells of known karyotype indicated that per-cell false-positive and false-negative rates are roughly equivalent to the 'gold standard' metaphase karyotype. The majority of the cells were run in parallel with a clinical commercial PGS service. Computed confidences were conservative and roughly concordant with accuracy. To examine ploidy in human embryos, the method was then applied to 26 disaggregated, cryopreserved, cleavage-stage embryos for a total of 134 single blastomeres. Only 23.1% of the embryos were euploid, though 46.2% of embryos were mosaic euploid. Mosaicism affected 57.7% of the embryos. Counts of mitotic and meiotic errors were roughly equivalent. Maternal meiotic trisomy predominated over paternal trisomy, and maternal meiotic trisomies were negatively predictive of mosaic euploid embryos. CONCLUSIONS: We have performed a major preclinical validation of a new method for PGS and found that the technology performs approximately as well as a metaphase karyotype. We also directly measured the mechanism of aneuploidy in cleavage-stage human embryos and found high rates and distinct patterns of mitotic and meiotic aneuploidy.

BACKGROUND: In natural conception only a few sperm cells reach the ampulla or the site of fertilization. This population is a selected group of cells since only motile cells can pass through cervical mucus and gain initial entry into the female reproductive tract. In animals, some studies indicate that the sperm selected by the reproductive tract and recovered from the uterus and the oviducts have higher fertilization rates but this is not a universal finding. Some species show less discrimination in sperm selection and abnormal sperm do arrive at the oviduct. In contrast, assisted reproductive technologies (ART) utilize a more random sperm population. In this review we contrast the journey of the spermatozoon in vivo and in vitro and discuss this in the context of developing new sperm preparation and selection techniques for ART. METHODS: A review of the literature examining characteristics of the spermatozoa selected in vivo is compared with recent developments in in vitro selection and preparation methods. Contrasts and similarities are presented. RESULTS AND CONCLUSIONS: New technologies are being developed to aid in the diagnosis, preparation and selection of spermatozoa in ART. To date progress has been frustrating and these methods have provided variable benefits in improving outcomes after ART. It is more likely that examining the mechanisms enforced by nature will provide valuable information in regard to sperm selection and preparation techniques in vitro. Identifying the properties of those spermatozoa which do reach the oviduct will also be important for the development of more effective tests of semen quality. In this review we examine the value of sperm selection to see how much guidance for ART can be gleaned from the natural selection processes in vivo.

As the COVID-19 pandemic spreads around the world, we are starting to see the first waves of epidemiological data1,2 and know that it disproportionately impacts older adults.3 However, with this still being a new and rapidly evolving global crisis, there is currently very little known about its broader impact on mental health. Clinicians are gaining early experiences around a range of issues that are highly relevant to the mental health care of older adults4 in the context of COVID-19. Retrospective studies of the 2003 SARS epidemic found that rates of suicide among older adults spiked during the period of the epidemic.

Discontinuation is a problem in fertility clinics. Many couples discontinue assisted reproductive technologies (ART) without achieving a live birth for reasons other than poor prognosis or the cost of treatment. Discontinuation has been attributed to the burden of treatment. The causes of burden can be broadly classified according to whether they originate in the patient, clinic or treatment. Interventions to alleviate these burdens include provision of comprehensive educational material, screening to identify highly distressed patients, provision of tailored coping tools and improvements in the clinic environment and medical interventions. Practical interventions to reduce the different causes of burden in ART exist, but further development and evaluation of the efficacy of these interventions requires more precise definition of terms and theory. In this paper, we propose a general integrated approach to cover different perspectives in dealing with burden in ART clinics. We firstly describe the integrated approach and present common sources of burden. We then describe interventions that could help reduce the burden in ART. Our paper is aimed at fertility clinic staff because of their day-to-day involvement with patients. However, this discussion should also be relevant to companies that develop treatments and to psychosocial experts. Reducing the burden of treatment should lead to improved outcomes, namely better quality of life during treatment and lower discontinuation rates.

The CRISPR-Cas9 system has the potential to revolutionize genome editing in human pluripotent stem cells (hPSCs), but its advantages and pitfalls are still poorly understood. We systematically tested the ability of CRISPR-Cas9 to mediate reporter gene knockin at 16 distinct genomic sites in hPSCs. We observed efficient gene targeting but found that targeted clones carried an unexpectedly high frequency of insertion and deletion (indel) mutations at both alleles of the targeted gene. These indels were induced by Cas9 nuclease, as well as Cas9-D10A single or dual nickases, and often disrupted gene function. To overcome this problem, we designed strategies to physically destroy or separate CRISPR target sites at the targeted allele and developed a bioinformatic pipeline to identify and eliminate clones harboring deleterious indels at the other allele. This two-pronged approach enables the reliable generation of knockin hPSC reporter cell lines free of unwanted mutations at the targeted locus.

BACKGROUND: The study goal was to develop and test the effectiveness of a brief online education and support program for female infertility patients. METHODS: A randomized-controlled trial was conducted. Using a Solomon-four group design, 190 female patients were recruited from three US fertility centers and were randomized into two experimental and two no-treatment control groups. The psychological outcomes assessed included infertility distress, infertility self-efficacy, decisional conflict, marital cohesion and coping style. Program dosage and satisfaction were also assessed at four weeks follow-up. RESULTS: Women exposed to the online program significantly improved in the area of social concerns (P = 0.038) related to infertility distress, and felt more informed about a medical decision with which they were contending (P = 0.037). Trends were observed for decreased global stress(P = 0.10), sexual concerns (P = 0.059), distress related to child-free living (P = 0.063), increased infertility self-efficacy (P = 0.067) and decision making clarity (P = 0.079). A dosage response was observed in the experimental groups for women who spent >60 min online for decreased global stress (P = 0.028) and increased self efficacy (P = 0.024). CONCLUSIONS: This evidence-based eHealth program for women experiencing infertility suggests that a web-based patient education intervention can have beneficial effects in several psychological domains and may be a cost effective resource for fertility practices.

Microsurgical epididymal sperm aspiration was a great advance in the therapy of patients with non-reconstructable, obstructive azoospermia, most notably congenital bilateral absence of the vas deferens. Using conventional in-vitro fertilization, pregnancies were rarely achieved because the rate of oocyte fertilization was extremely poor. However, the use of retrieved spermatozoa in conjunction with intracytoplasmic sperm injection (ICSI) has dramatically increased the likelihood of embryo formation. Typically, sperm and oocyte harvesting are performed simultaneously. We have investigated whether frozen-thawed spermatozoa work as well as fresh spermatozoa. When we had concluded from our own population of patients (groups I and II) that they did, we adopted a policy of aspirating spermatozoa, primarily cryopreserving them and using them for ICSI at a later date. We found the fertilization rates of this latter cohort of patients (group III) to be excellent (37% per oocyte), and the ongoing pregnancy rate is quite satisfactory (40% per couple, 29% per cycle). We offer this approach as an alternative to the traditional scheme because it markedly eases the burden of partner scheduling on both the couple and the clinicians involved. In addition, assurance of the availability of male partner spermatozoa can be attained prior to beginning ovulation induction.

OBJECTIVE: To estimate whether exercise before the first cycle of in vitro fertilization (IVF) affects cycle outcomes. METHODS: A total of 2,232 patients were prospectively enrolled before undergoing their first cycle of IVF for the treatment of infertility from 1994-2003 at three IVF clinics in the greater Boston area. The primary IVF outcomes of interest included successful live birth and four points of cycle failure: cycle cancellation, failed fertilization, implantation failure, and pregnancy loss. Unconditional logistic regression adjusting for observed confounders was used to quantify the relation between self-reported exercise and cycle outcome. RESULTS: In general, women who reported regular exercise were no more likely to have a live birth compared with those women who did not report exercise (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.7-1.0; P = .07). Women who reported exercising 4 hours or more per week for 1-9 years were 40% less likely to have a live birth (OR 0.6, CI 0.4-0.8) and were almost three times more likely to experience cycle cancellation (OR 2.8, CI 1.5-5.3) and twice as likely to have an implantation failure (OR 2.0, CI 1.4-3.1) or pregnancy loss (OR 2.0, CI 1.2-3.4) than women who did not report exercise. In general, women who participated in cardiovascular exercise had a 30% lower chance of successful live birth (OR 0.7, CI 0.6-0.9) than women who reported no exercise. CONCLUSION: Regular exercise before in vitro fertilization may negatively affect outcomes, especially in women who exercised 4 or more hours per week for 1-9 years and those who participated in cardiovascular exercise. LEVEL OF EVIDENCE: II-2.

Natural sperm selection in humans is a rigorous process resulting in the highest quality sperm reaching, and having an opportunity to fertilize, the oocyte. Relative to other mammalian species, the human ejaculate consists of a heterogeneous pool of sperm, varying in characteristics such as shape, size, and motility. Semen preparation in assisted reproductive technologies (ART) has long been performed using either a simple swim-up method or density gradients. Both methodologies provide highly motile sperm populations; however neither replicates the complex selection processes seen in nature. A number of methods have now been developed to mimic some of the natural selection processes that exist in the female reproductive tract. These methods attempt to select a better individual, or population of, spermatozoa when compared to classical methods of preparation. Of the approaches already tested, platforms based upon sperm membrane markers, such as hyaluronan or annexin V, have been used to either select or deselect sperm with varied success. One technology that utilizes the size, motility, and other characteristics of sperm to improve both semen analysis and sperm selection is microfluidics. Here, we sought to review the efficacy of both available and emerging techniques that aim to improve the quality of the sperm pool available for use in ART.

BACKGROUND: Infertility can significantly impact women's lives and personal relationships. Despite the negative impact of infertility, a significant number of women who are struggling to conceive do not consult a physician. This cross-sectional survey was conducted to determine the emotional impact of infertility on women to identify which aspects of fertility treatment contribute to the psychological stress experienced by so many patients and to identify barriers to seeking treatment. METHODS: Women (n = 445; 18-44 years) who had received fertility treatment within the past 2 years or were having trouble conceiving but had not received treatment, completed a 15-min survey online. RESULTS: Participants were from France (n = 108), Germany (n = 111), Italy (n = 112) and Spain (n = 114). Responses indicated that infertility causes a range of emotions and can strain relationships. Women who had received treatment were more likely to feel hopeful (26 versus 21%) and closer to their partner than women not in treatment (33 versus 19%, P < 0.05). Most women delayed starting treatment because of a desire to conceive naturally, and on the advice of physicians. Women aged ≥35 years took longer to seek help with their fertility issues. Injection-related anxiety was the second greatest barrier to treatment. CONCLUSIONS: This study has provided insight into the physical and psychological challenges of infertility treatments and permitted a better understanding of the factors that impact patient lives. A treatment protocol with minimal injections and provision of additional information may lessen the emotional impact and challenges of infertility and contribute to patient satisfaction with fertility treatment protocols.

The oxidation of phospholipid-bound docosahexaenoic acid (DHA) has been shown to be one of the major factors that limit the motile life span of sperm in vitro. Sperm samples show high cell-to-cell variability in life span and, consequently, in susceptibility toward lipid peroxidation. Therefore, we postulated that there is also cell-to-cell variability in DHA concentration in human spermatozoa. In this study, the concentration of DHA in subsets of human spermatozoa isolated by a discontinuous Percoll density gradient was determined by gas chromatography. Four subsets of human spermatozoa were isolated using a discontinuous Percoll gradient: fraction 1 was enriched in immature germ cells and immature sperm, fractions 2 and 3 contained, mostly, immature sperm with cytoplasmic droplets, and fraction 4 contained, for the most part, morphologically normal sperm, as determined by histochemical analysis. The results indicated that there were significant differences in DHA content in sperm from all 4 fractions. DHA content in sperm from fraction 1 was 2.5-fold higher than that found in fraction 4. DHA content in mouse sperm obtained from the seminiferous tubules was 3-fold higher than that found in mouse sperm obtained from the epididymis, consistent with the findings observed in ejaculated human sperm. The results of this study indicate (i) there is cell-to-cell variability in the concentration of DHA in human sperm and (ii) that there is a net decrease in DHA content in sperm during the process of sperm maturation.

STUDY QUESTION: What are the cohort trends of women undergoing oocyte cryopreservation (OC)? SUMMARY ANSWER: There has been a dramatic increase in OC cycles undertaken each year since 2010, and the demographics of women accessing OC has shifted to a younger age group, but so far very few women have returned to use their cryopreserved oocytes in treatments. WHAT IS KNOWN ALREADY: Although OC, as a method of fertility preservation, is offered around the world, global data are lacking on who is accessing OC, who is returning to thaw oocytes and whether these trends are changing. STUDY DESIGN, SIZE, DURATION: A trinational retrospective cohort study was performed of 31 191 OC cycles and 972 oocyte thaw (OT) cycles undertaken in the USA (2010-2016) and 3673 OC and 517 OT cycles undertaken in Australia/New Zealand (Aus/NZ; 2010-2015). PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were obtained from the USA Society for Assisted Reproductive Technology (SART) national registry and the Australian and New Zealand Assisted Reproduction Database (ANZARD). De-identified data were requested on all autologous oocyte freeze-all cycles and all cycles where autologous oocytes were thawed to be used in a treatment cycle for the time periods of interest. MAIN RESULTS AND THE ROLE OF CHANCE: In both the USA and Aus/NZ, there has been a dramatic rise in the number of OC cycles performed each year (+880% in the USA from 2010 to 2016 and +311% in Aus/NZ from 2010 to 2015). Across both regions, most women undergoing OC were aged in their late 30s, but the average age decreased over time (USA: 36.7 years vs 34.7 years in 2010 and 2016, respectively). The number of women returning for thaw cycles was low (USA: 413 in 2016, Aus/NZ: 141 in 2015) and most thaw cycles (47%) across both regions involved oocytes that were frozen for <6 months. In the USA, a higher proportion of cycles resulted in a live birth when only thawed oocytes were used, compared to cycles that combined thawed oocytes with fresh oocytes (25% vs 11%, respectively; P < 0.001). Age at retrieval influenced live birth rate in the USA; 38% of thaw cycles started in women who stored oocytes when aged ≤35 years resulted in a live birth, whereas only 16% resulted in a live birth for women who stored oocytes when aged ≥36 years. Similar data were unobtainable from Aus/NZ. LIMITATIONS, REASONS FOR CAUTION: There were limitations associated with both the SART and ANZARD data outputs received. The format in which the ANZARD data were provided, and the inconsistencies seen amongst cycle reporting in the SART dataset, restricted data interpretation. For example, both datasets did not provide a clear indication as to why women were undergoing OC and it was not possible to accurately calculate duration of storage for thaw cycles in the USA. We also did not obtain details on embryo quality from either database and acknowledge that embryo quality and subsequent outcome (embryo freezing or discard) would be of interest, especially when considering the efficacy of OC. WIDER IMPLICATIONS OF THE FINDINGS: The data show that there is widespread demand for OC, and it is increasingly undertaken by younger women; however, the limitations encountered in the dataset support the need for a shift to a more uniform approach to data collection and presentation by large databases, worldwide. STUDY FUNDING/COMPETING INTEREST(S): This study received funding from the Fertility Society of Australia to support the ANZARD data extraction. M.J. is supported by an Australian Government Research Training Program Scholarship stipend. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

STUDY QUESTION: What is the relationship between sperm DNA fragmentation and oxidative stress (OS) with increasing male age? SUMMARY ANSWER: Sperm DNA fragmentation increases with age and is likely related to both defective spermatogenesis and increasing OS levels. WHAT IS KNOWN ALREADY: Sperm quality declines with age. The presence of DNA damage in a high fraction of spermatozoa from a raw semen sample is associated with lower male fertility in natural conception and intrauterine insemination. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of 16 945 semen samples analysed at a single reference laboratory between January 2010 and December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: All males were undergoing an infertility evaluation. The cohort was divided into seven age categories: <30, 30-34, 35-39, 40-44, 45-49, 50 to <54 and ≥55 years. The mean age was 37.6 years (SD 6.8). Sperm DNA fragmentation index (DFI) and high DNA stainability (HDS) were calculated using flow cytometry. OS levels were measured using the oxidative stress adducts (OSA) test, by spectrophotometry. ANOVA with weighted polynomial contrast analysis was used to evaluate trends for DFI, OSA and HDS values across age categories. MAIN RESULTS AND THE ROLE OF CHANCE: Mean DFI significantly increased across all age groups (Ptrend < 0.001). OSA was lowest in patients <30 years old (mean 3.6, SD 1.0) and also increased as age increased (Ptrend < 0.001). There was a statistically significant difference between age groups for each of the three parameters (P < 0.001). There was a significant linear trend for DFI, OSA and HDS across the seven age categories (P < 0.001). Among patients with high DFI, there was a decreasing age-dependent trend in the patients observed with high OSA (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study. All males included in the study were undergoing a work-up for infertility and may not be representative of a fertile population. Additional patient demographics and clinical data were not available. WIDER IMPLICATIONS OF THE FINDINGS: DNA and/or oxidative damage in sperm may be just as important to understand as the chromosomal aberrations that are carried in the oocyte. Further studies are needed to evaluate the effect of advancing paternal age on the male genome and, ultimately, on the health of the offspring. STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained for this study. V.D. is an employee of Reprosource/Quest Diagnostics. D.S. reports he was a Scientific Advisor to Cooper Surgical. TRIAL REGISTRATION NUMBER: N/A.

PURPOSE OF REVIEW: Despite the promising success rates of IVF, many couples have to undergo several cycles before achieving live birth. In counseling patients faced with subfertility, it is important to provide cumulative live-birth rates. This review evaluates the current knowledge on cumulative rates, summarizing recently published evidence. RECENT FINDINGS: Existing data have been mostly presented in the form of live-birth rates per IVF cycle as a function of maternal age or reason for subfertility. Recent publications have been reporting IVF success rates in terms of cumulative live-birth rate (CLBR) per woman, thus providing a more realistic estimate that becomes applicable to individual couples. In general, CLBR following IVF has been reported between 45 and 55%. Maternal age has been shown to significantly reduce these rates, as has preimplantation genetic diagnosis. On the contrary, techniques mostly used to decrease the chance of multiple births, such as elective single embryo transfer and natural cycle IVF, do not affect CLBR while achieving a significant reduction in the rates of multiples. SUMMARY: Couples should be counseled that CLBR following IVF lies mostly around 50% and that maternal age as well as genetics of transferred embryos remain factors that influence success.

OBJECTIVE: To perform a series of analyses characterizing an artificial intelligence (AI) model for ranking blastocyst-stage embryos. The primary objective was to evaluate the benefit of the model for predicting clinical pregnancy, whereas the secondary objective was to identify limitations that may impact clinical use. DESIGN: Retrospective study. SETTING: Consortium of 11 assisted reproductive technology centers in the United States. PATIENT(S): Static images of 5,923 transferred blastocysts and 2,614 nontransferred aneuploid blastocysts. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Prediction of clinical pregnancy (fetal heartbeat). RESULT(S): The area under the curve of the AI model ranged from 0.6 to 0.7 and outperformed manual morphology grading overall and on a per-site basis. A bootstrapped study predicted improved pregnancy rates between +5% and +12% per site using AI compared with manual grading using an inverted microscope. One site that used a low-magnification stereo zoom microscope did not show predicted improvement with the AI. Visualization techniques and attribution algorithms revealed that the features learned by the AI model largely overlap with the features of manual grading systems. Two sources of bias relating to the type of microscope and presence of embryo holding micropipettes were identified and mitigated. The analysis of AI scores in relation to pregnancy rates showed that score differences of ≥0.1 (10%) correspond with improved pregnancy rates, whereas score differences of <0.1 may not be clinically meaningful. CONCLUSION(S): This study demonstrates the potential of AI for ranking blastocyst stage embryos and highlights potential limitations related to image quality, bias, and granularity of scores.

PURPOSE OF REVIEW: The goal of this review was to summarize the recent research on the relationship between stress and assisted reproductive technology treatment. RECENT FINDINGS: Women and men with infertility report high levels of distress that can impact their quality of life. There are numerous psychosocial interventions, including cognitive behavior therapy and/or self-help ones, which may decrease distress, increase patient retention and improve pregnancy rates. SUMMARY: Patient distress is an important factor to consider. Decreasing burden of care may lead to significant improvements in assisted reproductive technology outcome.