Expanding Our Reach: the Value of Massage Therapists in Melanoma Identification.

Massage therapists are uniquely positioned to identify skin cancer. Seminal work in 2013 revealed that 40% of massage therapists do not receive any training in skin cancer identification (Campbell et al. J Cancer Educ 28:158-164, 2013). Limited work has been published assessing optimal training methodologies to close this educational gap. We present the results of a study in which students were given access to a 30-min self-driven web-based learning module designed to teach the high yield points of melanoma demographics and clinical features. The students completed pre- and post-testing, the results of which indicated improved knowledge levels and improved confidence in detecting suspected melanoma. We conclude that a 30-min learning module may be sufficient to improve massage therapists' ability and comfort level in identifying melanoma. The ease of delivery of web-based modules may make this an important approach in ensuring that massage therapists receive basic training in skin cancer identification.

Association of Fresh Embryo Transfers Compared With Cryopreserved-Thawed Embryo Transfers With Live Birth Rate Among Women Undergoing Assisted Reproduction Using Freshly Retrieved Donor Oocytes.

IMPORTANCE: In in vitro fertilization cycles using autologous oocytes, data have demonstrated higher live birth rates following cryopreserved-thawed embryo transfers compared with fresh embryo transfers. It remains unknown if this association exists in cycles using freshly retrieved donor oocytes. OBJECTIVE: To test the hypothesis that in freshly retrieved donor oocyte cycles, a fresh embryo transfer is more likely to result in a live birth compared with a cryopreserved-thawed embryo transfer. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using national data collected from the Society for Assisted Reproductive Technology for 33 863 recipients undergoing fresh donor oocyte cycles in the US between January 1, 2014 and December 31, 2017. EXPOSURES: Fresh embryo transfer and cryopreserved-thawed embryo transfer. MAIN OUTCOMES AND MEASURES: The primary outcome was live birth rate; secondary outcomes were clinical pregnancy rate and miscarriage rate. Analyses were adjusted for donor age, day of embryo transfer, use of a gestational carrier, and assisted hatching. RESULTS: Recipients of fresh and cryopreserved-thawed embryos had comparable median age (42.0 [interquartile range {IQR}, 37.0-44.0] years vs 42.0 [IQR, 36.0-45.0] years), gravidity (1 [IQR, 0-2] vs 1 [IQR, 0-3]), parity (0 [IQR, 0-1] vs 1 [IQR, 0-1]), and body mass index (24.5 [IQR, 21.9-28.7] vs 24.4 [IQR, 21.6-28.7]). Of a total of 33 863 recipients who underwent 51 942 fresh donor oocyte cycles, there were 15 308 (29.5%) fresh embryo transfer cycles and 36 634 (70.5%) cryopreserved-thawed embryo transfer cycles. Blastocysts were transferred in 92.4% of fresh embryo transfer cycles and 96.5% of cryopreserved-thawed embryo transfer cycles, with no significant difference in the mean number of embryos transferred. Live birth rate following fresh embryo transfer vs cryopreserved-thawed embryo transfer was 56.6% vs 44.0% (absolute difference, 12.6% [95% CI, 11.7%-13.5%]; adjusted relative risk [aRR], 1.42 [95% CI, 1.39-1.46]). Clinical pregnancy rates were 66.7% vs 54.2%, respectively (absolute difference, 12.5% [95% CI, 11.6%-13.4%]; aRR, 1.34; [95% CI, 1.31-1.37]). Miscarriage rates were 9.3% vs 9.4%, respectively (absolute difference, 0.2% [95% CI, -0.4% to 0.7%]); aRR, 0.98 [95% CI, 0.91-1.07]). CONCLUSIONS AND RELEVANCE: In this retrospective cohort study of women undergoing assisted reproduction using freshly retrieved donor oocytes, the use of fresh embryo transfers compared with cryopreserved-thawed embryo transfers was associated with a higher live birth rate. However, interpretation of the findings is limited by the potential for selection and confounding bias.

Delta-9 THC can be detected and quantified in the semen of men who are chronic users of inhaled cannabis.

PURPOSE: The purpose of this proof-of-concept study was to determine whether delta-9-tetrahydrocannabinol (THC) and THC metabolites (11-OH THC and THC-COOH) can be detected in semen. METHODS: Twelve healthy men aged 18-45 years who identified as chronic and heavy users of inhaled cannabis were recruited. THC and THC metabolite levels were measured in serum, urine, and semen of the participants. Semen analyses were performed. Serum reproductive hormones were measured. RESULTS: The median age and BMI of participants were 27.0 years and 24.7 kg/m2, respectively. Over half the participants were daily users of cannabis for over 5 years. Serum reproductive hormones were generally within normal ranges, except prolactin, which was elevated in 6 of 12 participants (mean 13.9 ng/mL). The median sperm concentration, motility, and morphology were 75.5 million/mL, 69.5%, and 5.5%, respectively. Urinary THC-COOH was detected in all 12 participants, and at least one serum THC metabolite was present in 10 of 12 participants. Two semen samples had insufficient volume to be analyzed. THC was above the reporting level of 0.50 ng/mL in the semen of two of the remaining participants. Seminal THC was moderately correlated with serum levels of THC (r = 0.66), serum 11-OH THC (r = 0.57), and serum THC-COOH (r = 0.67). Seminal delta-9 THC was not correlated with urinary cannabinoid levels or semen analysis parameters. CONCLUSION: This is the first study to identify and quantify THC in human semen, demonstrating that THC can cross the blood-testis barrier in certain individuals. Seminal THC was found to be moderately correlated with serum THC and THC metabolites.

Abnormal human chorionic gonadotropin (hCG) trends after transfer of multiple embryos resulting in viable singleton pregnancies.

PURPOSE: The purpose of this study is to investigate whether abnormal hCG trends occur at a higher incidence among women conceiving singleton pregnancies following transfer of multiple (two or more) embryos (MET), as compared to those having a single embryo transfer (SET). METHODS: Retrospective cohort study was performed of women who conceived singleton pregnancies following fresh or frozen autologous IVF/ICSI cycles with day 3 or day 5 embryo transfers between 2007 and 2014 at a single academic medical center. Cycles resulting in one gestational sac on ultrasound followed by singleton live birth beyond 24 weeks of gestation were included. Logistic regression models adjusted a priori for patient age at oocyte retrieval and day of embryo transfer were used to estimate the Odds Ratio of having an abnormal hCG rise (defined as a rise or < 66% in 2 days) following SET as compared to MET. RESULTS: Among patients receiving two or more embryos, 6.1% (n = 84) had abnormal hCG rises between the first and second measurements, compared to 2.7% (n = 17) of patients undergoing SET (OR 2.16, 95% CI 1.26-3.71). Among patients with initially abnormal hCG rises who had a third level checked (89%), three-quarters had normal hCG rises between the second and third measurements. CONCLUSIONS: Patients who deliver singletons following MET were more likely to have suboptimal initial hCG rises, potentially due to transient implantation of other non-viable embryo(s). While useful for counseling, these findings should not change standard management of abnormal hCG rises following IVF. The third hCG measurements may clarify pregnancy prognosis.

The cost of a euploid embryo identified from preimplantation genetic testing for aneuploidy (PGT-A): a counseling tool.

PURPOSE: To determine the expected out-of-pocket costs of IVF with preimplantation genetic testing for aneuploidy (PGT-A) to attain a 50%, 75%, or 90% likelihood of a euploid blastocyst based on individual age and AMH, and develop a personalized counseling tool. METHODS: A cost analysis was performed and a counseling tool was developed using retrospective data from IVF cycles intended for PGT or blastocyst freeze-all between January 1, 2014 and August 31, 2017 (n = 330) and aggregate statistics on euploidy rates of > 149,000 embryos from CooperGenomics. Poisson regression was used to determine the number of biopsiable blastocysts obtained per cycle, based on age and AMH. The expected costs of attaining a 50%, 75%, and 90% likelihood of a euploid blastocyst were determined via 10,000 Monte Carlo simulations for each age and AMH combination, incorporating age-based euploidy rates and IVF/PGT-A cost assumptions. RESULTS: The cost to attain a 50% likelihood of a euploid blastocyst ranges from approximately $15,000 U.S. dollars (USD) for younger women with higher AMH values (≥ 2 ng/mL) to > $150,000 for the oldest women (44 years) with the lowest AMH values (< 0.1 ng/mL) in this cohort. The cost to attain a 75% versus 90% likelihood of a euploid blastocyst is similar (~ $16,000) for younger women with higher AMH values, but varies for the oldest women with low AMH values (~ $280,000 and > $450,000, respectively). A typical patient (36-37 years, AMH 2.5 ng/mL) should expect to spend ~ $30,000 for a 90% likelihood of attaining a euploid embryo. CONCLUSIONS: This tool can serve as a counseling adjunct by providing individualized cost information for patients regarding PGT-A.

Factors Associated with the Success of In Vitro Fertilization in Women with Inflammatory Bowel Disease.

BACKGROUND: It is unknown whether certain factors are associated with the success of in vitro fertilization (IVF) in women with inflammatory bowel disease (IBD). AIM: This study assessed whether certain characteristics are associated with greater success of live birth following IVF. METHODS: In a cohort study of 8684 women with IBD seen at two tertiary care centers, we identified 121 women with IBD who underwent IVF. We assessed the effect of numerous factors on likelihood of achieving live birth after IVF. RESULTS: Seventy-one patients with ulcerative colitis (UC) and 49 patients with Crohn's disease (CD) were analyzed. Patients with UC who achieved a live birth were younger (p = 0.03), had a shorter duration of disease (p = 0.01), and were more likely to be in remission (p = 0.03) versus those who did not achieve live birth. Patients with CD who achieved live birth were younger (p < 0.001), had lower body mass index (BMI) (p = 0.02), and had lower cycle day 3 follicle-stimulating hormone levels (p = 0.02). There was no difference in likelihood of achieving live birth among patients in remission and those with mild or unknown disease status (p = 0.69), though most CD patients (79.5 %) were in remission. Prior surgery was not associated with live birth in patients with UC (p = 0.31) or CD (p = 0.62). CONCLUSIONS: As in the general infertility population, younger patients and those with lower BMI were more likely to achieve live birth. History of surgery was not associated with live birth among IBD patients. This is important information for practitioners counseling IBD patients.

In Vitro Fertilization in Women With Inflammatory Bowel Disease Is as Successful as in Women From the General Infertility Population.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) affects women of reproductive age, so there are concerns about its effects on fertility. We investigated the success of in vitro fertilization (IVF) in patients with IBD compared with the general (non-IBD) IVF population. METHODS: We conducted a matched retrospective cohort study of female patients with IBD who underwent IVF from 1998 through 2011 at 2 tertiary care centers. Patients were matched 4:1 to those without IBD (controls). The primary outcome was the cumulative rate of live births after up to 6 cycles of IVF. Secondary outcomes included the proportion of patients who became pregnant and the rate of live births for each cycle. RESULTS: Forty-nine patients with Crohn's disease (CD), 71 patients with ulcerative colitis (UC), 1 patient with IBD-unclassified, and 470 controls underwent IVF during the study period. The cumulative rate of live births was 53% for controls, 69% for patients with UC (P = .08 compared with controls), and 57% for patients with CD (P = .87 compared with controls). The incidence of pregnancy after the first cycle of IVF was similar among controls (40.9%), patients with UC (49.3%; P = .18), and patients with CD (42.9%; P = .79). Similarly, the incidence of live births after the first cycle of IVF was similar among controls (30.2%), patients with UC (33.8%; P = .54), and patients with CD (30.6%; P = .95). CONCLUSIONS: Based on a matched cohort study, infertile women with IBD achieve a rate of live births after IVF that is comparable with those of infertile women without IBD.

In Vitro Fertilization Is Successful in Women With Ulcerative Colitis and Ileal Pouch Anal Anastomosis.

BACKGROUND: Women with ulcerative colitis (UC), who require ileal pouch anal anastomosis (IPAA), have up to a threefold increased incidence of infertility. To better counsel patients who require colectomy, we examined the success rates of in vitro fertilization (IVF) among women who have undergone IPAA. METHODS: This was a retrospective cohort study conducted at the Brigham and Women's Hospital and Beth Israel Deaconess Medical Center. Female patients with UC were identified via ICD-9 codes and cross-referenced with those presenting for IVF from 1998 through 2011. UC patients with IPAA were compared with the following two unexposed groups that underwent IVF: (1) patients with UC, who had not undergone IPAA, and (2) patients without inflammatory bowel disease (IBD). The primary outcome was the cumulative live birth rate. Secondary outcomes included number of oocytes retrieved, proportion of patients who underwent embryo transfer, pregnancy rate, and live birth rate at first cycle. RESULTS: There were 22 patients with UC and IPAA, 49 patients with UC and without IPAA, and 470 patients without IBD. The cumulative live birth rate after six cycles in the UC and IPAA groups was 64% (95% confidence interval (CI): 44-83%). This rate did not differ from the cumulative live birth rate in the UC without IPAA group (71%, 95% CI: 59-83%; P=0.63) or the group without IBD (53%, 95% CI: 48-57%; P=0.57). CONCLUSIONS: This study demonstrates that in our cohort, women who undergo IPAA achieve live births following IVF at comparable rates to women with UC without IPAA and to women without IBD.

The association between severe obesity and characteristics of failed fertilized oocytes.

STUDY QUESTION: Is the cytoskeletal and chromosomal organization of failed fertilized oocytes from severely obese patients (BMI ≥ 35 kg/m²) altered compared with that in patients with normal BMI (BMI 18.5-24.9 kg/m²)? SUMMARY ANSWER: Compared with normal BMI patients, severe obesity was associated with a greater prevalence of spindle anomalies and non-aligned chromosomes in failed fertilized oocytes. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Obesity is associated with poor reproductive outcomes, but little is known regarding the underlying mechanisms. To address potential mechanisms, our study compared the cytoskeletal and chromosome organization in failed fertilized oocytes from severely obese and normal BMI patients. DESIGN: The study population was drawn from IVF patients treated in a hospital-based infertility clinic between February 2010 and July 2011. The prevalence of meiotic spindle and chromosome alignment anomalies in failed fertilized oocytes from patients with severe obesity (i.e. Class II and III; BMI 35.0-50.1 kg/m²) was compared with those from patients with normal BMI (BMI 18.5-24.9 kg/m²). Oocytes were fixed and then labeled for tubulin, actin and chromatin. Spindle number and integrity, as well as chromosome alignment, were assessed using immunofluorescence microscopy and, in some cases, confocal microscopy. Generalized estimating equations were applied, which account for the correlation among oocytes from the same patient to estimate odds ratio (OR), 95% confidence intervals (CIs) and two-sided Wald P-values. Models were adjusted for continuous age at cycle start, cycle type (IVF or ICSI) and polycystic ovarian syndrome (PCOS) a priori. PARTICIPANTS AND SETTING: University-affiliated infertility clinic. A total of 276 oocytes that failed to fertilize from 137 patients were evaluated: 105 oocytes from severely obese women (n = 47) and 171 oocytes from normal BMI patients (n = 90). MAIN RESULTS AND THE ROLE OF CHANCE: (i) Significantly more oocytes from the severely obese group exhibited two spindles compared with those from the normal BMI group (58.9 versus 35.1%; OR = 2.68, CI = 1.39-5.15, P-value = 0.003). (ii) Among oocytes with a single spindle, those from severely obese patients showed a significantly higher prevalence of disarranged spindles with non-aligned chromosomes compared with those from normal BMI patients (28.6 versus 8.6%; OR = 4.58, CI = 1.05-19.86, P-value = 0.04). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: Inclusion of only failed fertilized oocytes, small sample size, unknown factors such as non-PCOS comorbidity. GENERALIZABILITY TO OTHER POPULATIONS: For this study, by design, it is unclear whether the findings are generalizable to successfully fertilized oocytes, and whether this oocyte-level influence of obesity is generalizable to infertile women who do not undergo stimulation or, more broadly, to spontaneous conceptions in fertile women. STUDY FUNDING/COMPETING INTEREST(S): none. TRIAL REGISTRATION NUMBER: n/a.

Cellular and genetic analysis of oocytes and embryos in a human case of spontaneous oocyte activation.

Unusual and consistent defects in infertility patients merit attention as these may indicate an underlying genetic abnormality, in turn necessitating tailored management strategies. We describe a case of repeated early pregnancy loss from in vivo conceptions, followed by cancelled embryo transfers after one IVF and one ICSI/PGD cycle. Following the unexpected presence of cleaved embryos at the fertilization check in the first IVF attempt, oocytes and embryos were subsequently analyzed in an ICSI/PGD case. Part of the oocyte cohort was fixed at retrieval for a cellular evaluation of microtubules, microfilaments and chromatin. The remaining oocytes were injected with sperm, and resultant embryos were biopsied for genetic analysis by fluorescence in situ hybridization (FISH), single-nucleotide polymorphism (SNP) microarray for 23 chromosome pairs, as well as with PCR for sex chromosomes. The presence of interphase microtubule networks and pronuclear structures indicated that oocytes were spontaneously activated by the time of retrieval. FISH revealed aneuploidy in all seven blastomeres analyzed, with all but two lacking Y chromosomes. Microarray SNP analysis showed an exclusively maternal origin of all blastomeres analyzed, which was further confirmed by PCR. From our multi-faceted analyses, we conclude that spontaneous activation, or parthenogenesis, was probably the pathology underlying our patient's recurrent inability to maintain a normal pregnancy. Such analyses may prove beneficial not only in diagnosing case-specific aberrations for other patients with similar or related failures, but also for furthering our general understanding of oocyte activation.

Diagnosing cellular defects in an unexplained case of total fertilization failure.

Despite the advent of ICSI, cases of total fertilization failure (TFF) often lead to cycle cancellation with limited diagnostic and therapeutic strategies currently available. We report on the case of an infertile couple who failed to conceive after repeated IVF and ICSI. Sperm of the husband were morphologically normal and passed a functional test assessing their ability to activate mouse oocytes. Whether oocytes were activated artificially with calcium ionophore after injection of husband's or with donor sperm, all oocytes failed to fertilize. Multiple polar bodies and two disorganized spindle structures were predominantly observed, pointing towards a cytoplasmic defect in the oocytes as the primary cause of the couple's infertility. In fact, injection of husband's sperm into donor oocytes resulted in the delivery of healthy twins. This report describes a course of action that may be applied for couples with TFF after both IVF and ICSI.

Secondary infertility and retained fetal bone fragments.

BACKGROUND: Retained fetal bone fragments may be an underreported and underappreciated cause of secondary infertility among women with an antecedent spontaneous or induced abortion. CASES: Three patients with a history of an antecedent induced abortion presented with secondary infertility. The infertility evaluation diagnosed retained intrauterine fetal bone fragments. After removal of the bone fragments, two of the three patients successfully conceived. CONCLUSION: Secondary infertility may be the only presenting symptom for women with retained fetal bone fragments. Women with secondary infertility and antecedent spontaneous or induced abortion may benefit from uterine evaluation with ultrasonography before initiating infertility treatment. For patients with findings of focal echogenic shadowing lesions at ultrasonography, we recommend ultrasonography-guided hysteroscopy to ensure that bone fragments embedded within the myometrium are not missed and are completely resected.

In vitro fertilization outcomes after transfer of embryos contaminated with yeast.

In this retrospective, matched-paired study, yeast in the embryo culture medium was associated with a trend toward decreased developmental competency that was more pronounced when observed early in culture. Because live births occurred after transfer of embryos in the yeast-contaminated group, we concluded that yeast contamination is not a reason to cancel embryo transfer (ET).

Coasting vs. cryopreservation of all embryos for prevention of ovarian hyperstimulation syndrome in in vitro fertilization.

In the patient at risk for ovarian hyperstimulation syndrome, coasting will result in fewer eggs retrieved and embryos produced when compared with cryopreservation of all embryos. However, both strategies are associated with a similar incidence of ovarian hyperstimulation syndrome, with achievement of comparable cumulative pregnancy rates.

Lesbian motherhood and genetic choices.

Rhonda, a physician, and Clara, a registered nurse, have been lovers for the past 7 years. Both women are in their 30s, in good health, and financially stable. Clara has contacted Dr. Robinson, a highly regarded obstetrician and geneticist, with an unusual request. Clara is seeking to become pregnant by means of in vitro fertilization (IVF) with an embryo transfer (ET) technology. She proposes being implanted with ova harvested from her partner, Rhonda, and fertilized in vitro with donor sperm from a local medical-school sperm bank. Dr. Robinson explains the relatively low success rate involved in IVF and ET techniques and suggests artificial insemination of Clara's own ova. Clara and Rhonda understand the low success rates but are undeterred. Their mutual goal is not merely to have a child but to share in the maternity of their children. What ethical issues are raised by the plan Clara and Rhonda propose? What are Dr. Robinson's ethical responsibilities with respect to the request by Clara and Rhonda?

The role of preparatory cycles in ovum donation recipients: a retrospective study.

PURPOSE: To determine whether preparatory cycles affect in vitro fertilization (IVF) outcome in ovum donation. METHODS: Medical records of 98 ovum donation recipients undergoing their first egg donation cycle were analyzed retrospectively. Preparatory cycles were performed in 50 patients with leuprolide acetate, estrogen, and progesterone. An endometrial biopsy was performed on day 10-12 of progesterone supplementation, to determine adequacy of the preparatory cycle. RESULTS: Pregnancy rates in women with and without preparatory cycles were 42.0% and 43.8%, respectively. Among ovum donation recipients who underwent preparatory cycles, the percentages of adequate endometrial biopsies in pregnant versus nonpregnant groups were 76.2% and 84.3%, respectively. No results showed statistical significance. CONCLUSIONS: Preparatory cycles do not increase pregnancy rates in ovum donation recipients. In addition, no correlation was noted between adequate endometrial biopsies and higher pregnancy rates.