Seeking Fertility Treatment Research Articles

Length-biased semi-competing risks models for cross-sectional data: an application to current duration of pregnancy attempt data.

Cross-sectional length-biased data arise from questions on the at-risk time for an event of interest from those who are at-risk but have yet to experience the event. For example, in the National Survey on Family Growth (NSFG), women who were currently attempting to become pregnant were asked how long they had been attempting pregnancy. Cross-sectional survival analysis methods use the observed at-risk times to make inference on the distribution of the unobserved time-to-failure. However, methodological gaps in these methods remain such as how to handle semi-competing risks. For example, if the women attempting pregnancy had undergone fertility treatment during their current pregnancy attempt. In this paper, we develop statistical methods that extend cross-sectional survival analysis methods to incorporate semi-competing risks. They can be used to estimate the distribution of the length of natural pregnancy attempts (i.e., without fertility treatment) while correctly accounting for women that sought fertility treatment prior to being sampled using cross-sectional data. We demonstrate our approach based on simulated data and an analysis of data from the NSFG. The proposed method results in separate survival curves for: time-to-natural-pregnancy, time-to-fertility treatment, and time-to-pregnancy after fertility treatment.

Expression of obesity-related genes in human spermatozoa affects the outcomes of reproductive treatments

To study the abundance of obesity-related gene (ORG) mRNA in human spermatozoa and its association with sperm quality parameters, embryonic development, and pregnancy rates after assisted reproduction treatment (ART). Cross-sectional study of spermatozoa ORG mRNA expression, and sperm and embryonic development parameters of infertile couples attending a single ART center. University, in collaboration with a medically assisted reproduction center. One hundred six couples seeking fertility treatment and receiving ART. Expression of spermatozoa ORG mRNA was assessed by quantitative reverse transcription-polymerase chain reaction. Sperm and embryonic development parameters were measured by board-certified embryologists. Serum β-human chorionic gonadotropin levels and fetal heartbeat detection on ultrasound were used to document biochemical and clinical pregnancy, respectively. Correlations between the abundance of ORG transcripts in spermatozoa and sperm quality, embryonic development, and achievement of pregnancy. The abundance of spermatozoa FTO mRNA was positively correlated with total sperm count (r = 0.5030), fertilization rate (r = 0.4854), embryo cleavage rate (r = 0.5705), and high-quality embryo rate (r = 0.6982). The abundance of spermatozoa MC4R transcript was negatively correlated with sperm viability (r = -0.3111) and positively correlated with biochemical pregnancy (r = 0.4420). The abundance of MC4R and GNPDA2 transcripts was higher in spermatozoa of men with asthenozoospermia and teratozoospermia than in those with normozoospermia. To our knowledge, this is the first report showing that the abundance of MC4R and FTO transcripts in spermatozoa is associated with sperm and embryo quality parameters, as well as pregnancy rates. Overall, these results further support the view that male factors beyond classic sperm quality parameters, namely the abundance of ORG transcripts, also affect the outcome of ART.

Infertility in the Midwest: perceptions and attitudes of current treatment

Although infertility affects an estimated 6.1 million individuals in the United States, only half of those individuals seek fertility treatment and the majority of those patients are White and of high socioeconomic status. Research has shown that insurance mandates are not enough to ensure equal access. Many workplaces, schools, and medical education programs have made efforts in recent years to improve the cultural humility of providers in efforts to engage more racially and economically underrepresented groups in medical care. However, these efforts have not been assessed on a population of patients receiving fertility care, an experience that is uniquely shaped by individual social, cultural, and economic factors. This study aimed to better understand the racial, cultural, economic, and religious factors that impact patient experiences obtaining fertility care. A cross-sectional self-administered survey was administered at an academic fertility center in Chicago, Illinois. Of 5000 consecutive fertility care patients, 1460 completed the survey and were included in the study sample. No interventions were used. Descriptive univariate frequencies and percentages were calculated to summarize sociodemographic and other relevant patient characteristics (eg, race or ethnicity, age, household income, religious affiliation, insurance coverage). Rates of endorsing perceived physician cultural competency were compared among demographic subgroups using Pearson chi-squared tests with 2-sided P<.05 indicative of statistical significance. To identify the key determinants of patient-reported worry regarding 9 different fertility treatment outcomes and related concerns, a series of multiple logistic regression models were fit to examine factors associated with patient report of being "very worried" or "extremely worried." Members of our sample (N=1460) were between 20 and 58 years of age (meanadjusted, 36.2; standard deviation, 4.4). Among Black participants, 42.3% reported that their physician does not understand their cultural background compared with 16.5% of White participants (P<.0001). Participants who identified as Latinx were significantly more likely than White participants to report being very/extremely worried about side effects of treatment, a miscarriage, ectopic pregnancies, and birth defects (P<.05, P=.02, P=.002, P=.001, respectively). Individuals who identify as Hindu were nearly 4 times more likely to report being very/extremely worried about experiencing an ectopic pregnancy than nonreligious participants (P<.0002). Respondents most strongly identified the biology or physiology of the couple (meanadjusted, 21.6; confidence interval, 20.4-22.7) and timing or age (meanadjusted, 27.8; confidence interval, 26.5-29.1) as being associated with fertility. Overall, respondents most strongly disagreed that the ability to bear children rests upon God's will (meanadjusted, 65.4; confidence interval, 63.7-67.1), which differed most significantly by race (P<.0001) and religion (P<.0001). Of the patient characteristics investigated, racial and ethnic subgroups showed the greatest degree of variation in regard to worries and concerns surrounding the experience of fertility treatment. Our findings emphasize a need for improved cultural humility on behalf of physicians, in addition to affordable psychological support for all patients seeking fertility care.

Hysterosalpigography findings of female partners of infertile couple attending fertility clinic at Lagos University Teaching Hospital

IntroductionHysterosalpingography (HSG) is an outpatient fluoroscopic method for the evaluation of the uterine cavity, fallopian tubes, and the surrounding peritoneal cavity. Female fertility depends greatly on normal female reproductive organs; hence tubal abnormalities may contribute significantly to female infertility. HSG is an invaluable screening tool in the evaluation of women with suspected tubal factor infertility. This study aims to review the HSG findings of women who sought fertility treatment at the Lagos University Teaching Hospital, Lagos (LUTH).Methodsthis was a retrospective study of the pattern of HSG findings among female partners of infertile couples seeking fertility treatment at the LUTH, over a 2-year period, from January 2018 to December 2019.Resultsa total of 266 medical records and HSG results were reviewed and included in the data analysis. The mean age (± standard deviation) was 38.4 (± 0.3) years with a range of 24 to 50 years. Most (80.5%) of the participants have secondary infertility and majority (65.4%) were nulliparous. Tubal pathology was the commonest abnormality detected on HSG in 54.9% of women. About one-third (30.8%) of women had bilateral tubal occlusion on HSG. With regards to the right fallopian tube, 43.2% of the participants had tubal occlusion, which differs from 41.7% on the left fallopian tube. Similarly, 10.2% of the women had hydrosalpinx on the left tube when compared with 9% on the right tube. Age (OR 1.055; 95% CI: 1.006, 1.106, p-value 0.028), and previous salpingectomy [OR 6.151; 95% CI: 1.335, 28.349] and myomectomy [OR 4.6; 95% CI: 1.814, 11.67] were identified as risk factors for tubal pathologies on HSG.Conclusiontubal abnormalities are common findings on HSG and the identifiable risk factors for tubal pathologies include age, salpingectomy, and myomectomy. HSG remains a vital screening tool in the evaluation of tubal-factor infertility in Nigeria.

Women’s Knowledge and Awareness of the Effect of Age on Fertility in Kazakhstan

An accurate understanding of reproductive facts is essential for appropriate decision making regarding whether, when, and how to conceive. The objective of this study was to investigate women’s knowledge of how age affects fertility and their knowledge about the effectiveness for assisted reproductive technologies for treating fertility. A cross-sectional study was conducted including women seeking fertility treatment at the University Medical Center, Nur-Sultan, Kazakhstan in 2018–2019. Patients were interviewed with a structured questionnaire. Socio-demographic, clinical characteristics, and knowledge and awareness about the implications of aging for fertility (advanced maternal age (AMA)) and pregnancy outcomes using fertility treatments (assisted reproductive technologies ((ART)) and the sum of both scores total knowledge score (TKS). TKS mean was 7.7 (SD = 2.1), AMA was 5.0 (SD = 1.5), and ART was 2.7 (SD = 1.5). No socio-demographic factors correlated with lower knowledge. Fertility knowledge was found to be low. No differences were found associated with socio-economic level, although they were identified in women with certain types of infertility and a history of gynecological problems. Delaying childbearing based on incorrect perceptions of female fertility could lead to involuntary childlessness. Health education regarding fertility has to be part of broader health promotion programs to enhance awareness of the effect of age on fertility.

Prevalence of Blood-Borne Viral Infections (HIV, HBV, HCV) Among People Seeking Fertility Services in Ontario, Canada

IntroductionThe Applied Health Research Question (AHRQ) portfolio is an initiative funded by the Ontario Ministry of Health. Knowledge users submit AHRQ requests to use administrative health data to inform their planning, policy and program development.&#x0D; Objectives and ApproachA request to estimate prevalence and incidence of blood-borne viral infections (BBVI) among individuals seeking fertility treatment services was approved by the ICES AHRQ team. To determine whether current BBVI testing guidelines are effective for timely identification of BBVI among individuals undergoing fertility treatment, this AHRQ sought to estimate: a) the testing prevalence for BBVI (using viral hepatitis as a proxy for all BBVI including HIV), and b) BBVI incidence over a five-year follow-up period. We used infertility codes billed by gynecologists and urologists to identify individuals seeking fertility treatment between April 1, 2002 and March 31, 2013. We looked forward five years from a first BBVI test billed by a physician and assessed annual and cumulative testing prevalence and incidence of viral hepatitis and HIV using rule-based administrative algorithms.&#x0D; ResultsIn total, 184,328 individuals (61.6% female) were included. The five-year BBVI testing prevalence was 45.5% and the median number of tests was 2 (interquartile range: 2-3). An estimated 949 new cases (48% diagnosed within 12 months of first BBVI test) of viral hepatitis were identified in the five-year follow-up with a cumulative incidence of 522 (95%CI 489-556) per 100,000 population. There were 57 new HIV cases (68% diagnosed within 12 months of first BBVI test) with a cumulative incidence of 31.4 (95%CI 23.7-40.6) per 100,000. The median times from first BBVI test to hepatitis and HIV diagnoses were 13.0 months (IQR 2.33-32.2) and 3.0 months (IQR 1.34-20.0), respectively.&#x0D; Conclusion / ImplicationsThese findings can be used to develop evidence-based BBVI testing guidelines for individuals seeking fertility treatment services.

Air pollution and anti-Müllerian hormone concentrations in the Sister Study

Background: Anti-Müllerian hormone (AMH) levels are a marker of ovarian reserve and are indicative of a woman’s reproductive life span. Although exposure to indoor air pollution has been associated with diminished AMH, little is known about the association between ambient air pollution and ovarian reserve especially in a population not seeking fertility treatments. Methods: For 4,696 Sister Study participants, residential annual average exposure to PM2.5, PM10 , and NO2 was assessed using land-use regression models and kriging. We estimated distance to the nearest major road for both adult and childhood residences. Serum AMH was measured using ultrasensitive AMH ELISA and picoAMH ELISA kits in 1,322 premenopausal women. We also included postmenopausal women (N = 3,374) in our analyses to address potential selection bias. Inverse probability weighting was used to account for selection into the study. For postmenopausal women or women with AMH values below the limit of detection (LOD), AMH values were imputed as LOD/2. To account for the non-detects, reverse Cox regression modeling with restricted cubic spline adjustment for age was used to estimate hazard ratios (HRs) for the association between ambient air pollution and distance to major roadway and AMH levels. Results: Overall, we saw no consistent association between air pollution exposure or proximity to roadways and AMH levels. An interquartile range (IQR) increase in NO2 was associated with slightly higher AMH levels (HR = 1.10, 95% CI: 0.99, 1.22). However, among the women not currently using oral contraceptives (which may impact measured AMH levels), an IQR increase in PM2.5 was associated with lower AMH levels (HR = 0.88, 95% CI: 0.77-0.99). Conclusions: We saw little evidence to support an association between outdoor air pollution and diminished ovarian reserve in women of older reproductive age, except possibly among women who were not current users of hormonal contraceptives.

Sperm mitochondrial DNA biomarkers and couple fecundity.

Do sperm mitochondrial DNA measures predict probability of pregnancy among couples in the general population? Those with high sperm mitochondrial DNA copy number (mtDNAcn) had as much as 50% lower odds of cycle-specific pregnancy, and 18% lower probability of pregnancy within 12 months. Semen parameters have been found to poorly predict reproductive success yet are the most prevalent diagnostic tool for male infertility. Increased sperm mtDNAcn and mitochondrial DNA deletions (mtDNAdel) have been associated with decreased semen quality and lower odds of fertilization in men seeking fertility treatment. A population-based prospective cohort study of couples discontinuing contraception to become pregnant recruited from 16 US counties from 2005 to 2009 followed for up to 16 months. Sperm mtDNAcn and mtDNAdel from 384 semen samples were assessed via triplex probe-based quantitative PCR. Probability of pregnancy within 1 year was compared by mitochondrial DNA, and discrete-time proportional hazards models were used to evaluate the relations with time-to-pregnancy (TTP) with adjustment for covariates. Higher sperm mtDNAcn was associated with lower pregnancy probability within 12 months and longer TTP. In unadjusted comparisons by quartile (Q), those in Q4 had a pregnancy probability of 63.5% (95% CI: 53.1% to 73.1%) compared to 82.3% (95% CI: 73.2% to 89.9%) for Q1 (P = 0.002). Similar results were observed in survival analyses adjusting for covariates to estimate fecundability odds ratios (FORs) comparing mtDNAcn in quartiles. Relative to those in Q1 of mtDNAcn, FORs (95% CI) were for Q2 of 0.78 (0.52 to 1.16), Q3 of 0.65 (0.44 to 0.96) and Q4 of 0.55 (0.37 to 0.81), and this trend of decreasing fecundability with increasing mtDNAcn quartile was statistically significant (FOR per log mtDNAcn = 0.37; P < 0.001). Sperm mtDNAdel was not associated with TTP. This prospective cohort study consisted primarily of Caucasian men and women and thus large diverse cohorts are necessary to confirm the associations between sperm mtDNAcn and couple pregnancy success in other races/ethnicities. Our results demonstrate that sperm mtDNAcn has utility as a biomarker of male reproductive health and probability of pregnancy success in the general population. This work was funded in part by the National Institute of Environmental Health Sciences, National Institutes of Health (R01-ES028298; PI: J.R.P.) and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contracts N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). The authors declare no competing interests. N/A.

Association of personal exposure to power-frequency magnetic fields with pregnancy outcomes among women seeking fertility treatment in a longitudinal cohort study

To assess for the first time the potential relationships of personal exposure to magnetic fields (MF) with pregnancy outcomes among a cohort of women from a fertility clinic, addressing, through study design, some of the primary limitations of previous studies on this topic. Longitudinal preconception prospective cohort. Fertility center. Our analysis included 119 women recruited from 2012 to 2018, who underwent invitro fertilization (IVF) (n = 163 cycles) and/or intrauterine insemination (IUI) (n = 123 cycles). Women wore personal exposure monitors continuously for up to three consecutive 24-hour time periods separated by several weeks. Implantation, clinical pregnancy, live birth, and pregnancy loss. The median and maximum of the overall daily mean (daily peak) MF exposure levels were 1.10 mG (2.14 mG) and 15.54 mG (58.73 mG), respectively. MF exposure metrics were highest among women who changed environments four or more times per day. Overall, no statistically significant associations between MF exposure metrics and fertility treatment or pregnancy outcomes were observed in crude or adjusted models. Effect estimates, both positive and negative, varied by outcome and the exposure metric, including the way in which exposure was modeled. Personal MF exposures were not associated with fertility treatment outcomes or pregnancy outcomes. Despite its limited size, strengths of the study include a longitudinal repeated-measures design, the collection of personal MF exposure data across multiple days, and carefully documented outcome and covariate information among a potentially susceptible study population.

Reproductive outcomes associated with flame retardants among couples seeking fertility treatment: A paternal perspective

BackgroundPolybrominated diphenyl ethers (PBDEs) have been phased out of production for nearly a decade yet are still frequently detected in serum of U.S. adults. PBDE concentrations have been associated with adverse reproductive outcomes and laboratory studies suggest hydroxylated-BDEs (OH-BDEs) may act as endocrine disruptors. We set out to assess the joint effects of paternal and maternal serum PBDE concentrations on in vitro fertilization (IVF) outcomes and the association between paternal serum OH-BDE concentrations and IVF outcomes. MethodsThis analysis included 189 couples (contributing 285 IVF cycles) recruited between 2006 and 2016 from a longitudinal cohort based at Massachusetts General Hospital Fertility Center who completed at least one IVF cycle and had an available blood sample at study entry. Congeners (47, 99, 100, 153, and 154) and OH-BDEs (3-OH-BDE47, 5-OH-BDE47, 6-OH-BDE47 and 4-OH-BDE49) were quantified in serum. Log-transformed PBDEs and OH-BDEs were modeled in quartiles for associations with IVF outcomes using multivariable generalized mixed models and cluster weighted generalized estimating equations. ResultsLipid-adjusted concentrations of PBDEs and OH-BDEs were higher in females than in male partners. There were no clear patterns of increases in risk of adverse IVF outcomes associated with PBDEs and OH-BDEs. However, some decreases in associations with IVF outcomes were observed in isolated quartiles. ConclusionsOur assessment of couple level exposure is unique and highlights the importance of including male and female exposures in the assessment of the influence of environmental toxicants on pregnancy outcomes.

Association of Alcohol Intake and Semen Parameters in Men With Primary and Secondary Infertility: A Cross-Sectional Study.

Alcohol consumption has commonly been associated with semen parameters. However, the association between alcohol intake and semen parameters in primary and secondary infertile men remains unclear. In this study, 776 infertile men from China were grouped according to alcohol intake: abstainers, moderate drinkers (<9 units/week, up to approximately 100 g of ethanol) and heavy drinkers (≥9 units/week). Semen parameters, including semen volume, sperm concentration, total sperm count, progressive motility and normal morphology were investigated. Alcohol consumption and other lifestyle factors were assessed by questionnaire. Logistic regression models were applied. There was no significant association between alcohol consumption and semen parameters in men with primary infertility. Smaller testis volumes and lower sperm concentrations were found among moderate and heavy drinkers in the secondary infertility group than among abstainers. After adjustment for potential confounders, men with secondary infertility and heavy alcohol consumption had a higher risk of abnormal sperm concentrations (OR = 3.72; 95% CI, 1.04, 13.37). These findings suggest that alcohol intake may decrease sperm concentrations in men with secondary infertility, whereas no association was found in men with primary infertility. It may be beneficial for clinicians to advise male patients with secondary infertility who are seeking fertility treatment to avoid heavy alcohol consumption.

IMPACT OF COVID-19 ON QUALITY OF LIFE AND PATIENT SATISFACTION AMONGST PATIENTS SEEKING FERTILITY EVALUATION AND TREATMENT

The purpose of this study was to assess the effect of the pause on fertility treatments, due to the COVID-19 pandemic, on patients’ fertility quality of life (FQoL). Web-based survey. Patients seeking fertility care at a single academic fertility center from 1/2020 - 3/2020 with valid email addresses were surveyed. Patient demographics, evaluation or treatment type, history, satisfaction with newly instituted TeleHealth, viewpoint on ASRM guidance, and an adapted version of the validated Fertility Quality of Life Questionnaire (FQoL) were assessed. FQoL score was the primary outcome and was used to quantitatively assess the impact of COVID-19 on patients’ FQoL. Student’s T-tests were used to compare FQoL scores between patients who experienced a delay in evaluation or treatment vs. those who did not. Four hundred fifty-six patients received a survey link and 38.8% (177/456) responded. The most common delayed treatments were intrauterine inseminations (36.0%), frozen embryo transfers (35.2%), and oocyte retrievals (26.4%). 37.3% (66/177) of patients had a TeleHealth appointment with a provider. The majority (90.9%) were dissatisfied with their encounter; however, 42.4% would consider utilizing TeleHealth in the future. Of 125 patients who experienced delays, 12.8% agreed with the decision to pause treatments and 41.6% disagreed. The remaining 45.6% patients neither agreed nor disagreed. Of the 54.2% (96/177) of patients that completed the adapted FQoL survey in its entirety, those with delayed fertility evaluation or treatment (n=77) had significantly lower mean FQoL scores than those who did not experience a delay (76.6 vs 86.5, p=0.01). 52% of patients who completed FQoL questions agreed with the pause of fertility treatments; they had significantly higher FQoL scores than those who disagreed (82.0 vs. 71.8, p<0.005).Tabled 1No Delay (n=52)Delay (n=125)P valueAverage FQoL average*86.576.60.01% Utilized TeleHealth23.143.20.01% Desires future TeleHealth32.750.4<0.01% Impartial or agreed with treatment pause30.848.0<0.01*Data from 96 patients who completed FQOL questions. Open table in a new tab *Data from 96 patients who completed FQOL questions. Patients who experienced delays in fertility care due to COVID-19 reported lower FQoL compared to those who did not. Less than half of patients agreed with guidance suggesting a delay in treatments, despite continued access to care via TeleHealth. Although efforts were made to maintain open lines of communication and patient access to care during the pandemic via TeleHealth, the majority of patients were dissatisfied with their experience, regardless of delays. In spite of their experience, nearly half of participants expressed interest in using TeleHealth for future fertility care.

TELEMEDICINE AND AT-HOME IVF KIT: NOVEL APPLICATION DURING THE COVID-19 PANDEMIC

During the COVID-19 pandemic, access to fertility has been difficult due to fear of contracting the virus. Many patients, especially those with diminished ovarian reserve (DOR), strongly desire to pursue their fertility treatments that include oocyte and/or embryo freezing for fertility preservation because it is a time-sensitive matter fearing the loss of all their ovarian reserve. Given this challenging situation and in order to minimize the repeated office visits for monitoring during an IVF cycle, we aimed to test the efficacy of a new modality for IVF treatment using telemedicine and a patented kit called At-HOME IVF kit. Large fertility clinic with university affiliation. A retrospective study assessed the outcome of using telemedicine with At-HOME IVF kit in patients who have DOR (n=22) based on previous history of poor ovarian response, previously documented low serum anti-Mullerian hormone (<1 ng/mL), elevated day 3 follicle-stimulating hormone (>10 mIU/mL), or low antral follicle count (<8). Patients desired either embryo (n=17) or oocyte (n=5) freezing. Telemedicine was used for consultation in order to reduce the total waiting time for seeking fertility treatment and to minimize office visits. The kit was mailed to the patient's home, contained no injectable medications and contained all the necessary medications needed for ovarian stimulation, ovulation suppression, and oocyte maturation trigger. The oral pills were clomid 100 mg taken from cycle day 3 until cycle day 11 and letrozole 5 mg taken from cycle day 3 until cycle day 7, the vaginal pill was the GnRH antagonist (Elagolix) 50 mg taken on cycle days 9 and 11, and nasal spray (lupron 30 IU) taken on cycle days 12 and 13. Oocyte retrieval was then performed on cycle day 14. Each patient took the medications included in the kit without office visits for monitoring and presented only on the day of the oocyte retrieval. The main outcome included the number of oocytes and embryos (cleavage-stage or blastocyst-stage) cryopreserved. Because of the COVID-19 pandemic, embryo transfer was not currently recommended or performed. Data are presented as mean ± sem. The mean age of the participants was 39.9 ± 0.9 years. Upon presentation on the day of oocyte retrieval, blood hormonal testing and transvaginal ultrasound showed that none of the patients had ovulated and that all patients had appropriate ovarian stimulation response with the number of mature follicles (>18mm) up to 8 (3.3 ± 0.4). All patients underwent oocyte retrieval with 21 out of 22 patients having up to 8 mature oocytes collected (2.4 ± 0.4). Ten out of 17 patients who underwent IVF had up to 4 embryos cryopreserved at either the cleavage-stage or blastocyst stage. During the global health emergency and current/future pandemics due to a highly transmissible infectious organism, oocyte and embryo cryopreservation can be performed without frequent monitoring and without the injectable medications using At-HOME IVF kit. This will allow patients with DOR the possibility of proceeding with fertility treatments with minimum exposure to office visits.

The prevalence, promotion and pricing of three IVF add-ons on fertility clinic websites

Research questionHow are IVF clinic websites advertising three common IVF add-ons: assisted hatching, time-lapse embryo imaging and preimplantation genetic testing for aneuploidies (PGT-A)? DesignThe Human Fertilisation and Embryology Authority ‘Choose a fertility clinic‘ website service was used to identify IVF clinics and their websites. Assisted hatching, time-lapse embryo imaging and PGT-A were examined to determine which websites advertised them, what price they charged and what claims they made in relation to the add-ons. ResultsEighty-seven eligible clinics were identified, with 72 unique websites; 37 (43%) clinics were part of one of nine groups of IVF clinics, of sizes ranging from two to eight clinics in the UK. Time-lapse imaging (TLI) was the most frequently advertised of the three add-ons (67% of clinics), followed by PGT-A (47%) and assisted hatching (28%). Very few websites stated that the effectiveness of the add-on was in doubt or unclear (four, two and one websites for TLI, PGT-A and assisted hatching, respectively), and none raised the possibility that an add-on might have negative effects. Claims of efficacy were often based on upstream outcomes (e.g. implantation, pregnancy). Some claims that PGT-A and TLI improved live birth rates were found. There was substantial variation in pricing. ConclusionsIVF clinic websites provide valuable information for patients seeking fertility treatment so it is key that the information is accurate and complete. There is a need for transparent information on interventions, including uncertainties and risks, to be made available by IVF clinics to support well-informed treatment decisions. The selected add-ons are widely advertised, and there is wide variation in pricing.

Coital Frequency and the Probability of Pregnancy in Couples Trying to Conceive Their First Child: A Prospective Cohort Study in Japan.

Background: Low fertility persists but remains unexplained in Japan. We examined whether the probability of pregnancy was influenced by coital frequency, age, reproductive age (assessed by antimüllerian hormone, AMH), and BMI. Methods: We established a two-year prospective study with a sample of hormonally monitored Japanese women aged 23–34 years wanting to conceive their first child. For a maximum of 24 weeks participants recorded menstrual bleeding, sexual intercourse, ovulation, and pregnancy. Additional information on pregnancy and infertility treatment was collected one and two years after intake. Results: The natural conception rate and coital frequency were both low in this sample. Among 80 participants, 44% (35) naturally conceived in 24 weeks. After two years, 74% (59) of women had delivered or were currently pregnant, 50% (40) due to natural and 24% (19) due to assisted conception, and 5% (4) were lost to follow-up. By two years, 56% (45) of women had sought fertility treatment. In 18% (58/319) of the observed ovarian cycles across 24 weeks there was no intercourse in a fertile period. Higher coital frequency at intake was associated with increased probability of conception by 24 weeks of follow-up (OR 1.23, 95%CI 1.02, 1.47). Chronological age, reproductive age, and BMI were not associated with the probability of pregnancy at 24 weeks. Conclusions: Our results suggest that first, natural conception rates could potentially increase with more frequent and well timed intercourse, and second that further work is needed to understand why even in a motivated sample of women monitoring their fertile periods, both the conception and coitus rates were low.

Endometrioma surgery and possibilities of early disease control

Aim: The purpose of this study is to investigate the efficacy of surgical management in ovarian endometrioma for early disease control and long-term fertility preservation in adolescents and women of very young age. A history of cyclic pains in adolescents is highly associated with endometriosis. Sonography enables the diagnosis of small endometriomas 1-2 cm in diameter. Although it is obvious that the risk of damage to normal ovarian tissue is diminished when operating and removing a 2 cm endometrioma, it is not approved since there are currently no tools available to identify at-risk patients. Additionally, performing laparoscopic surgery with 5 mm instruments in patients with small endometriomas will likely cause more harm than benefit. Methods: A literature review was performed using key words for endometrioma surgery, in vitro fertilization (IVF), implantation rate, pregnancy rate and adolescents. The pros and cons of surgical removal prior to assisted reproductive therapy (ART), outcomes of endometrioma surgical treatment before IVF, and current recommendations for endometrioma removal were investigated. Results: The total patient population from articles supporting removal of endometrioma before assisted reproductive therapy and evidence against were 30,741 and 9983 respectively. However, the only study reporting a statistically significant result found an 8.2% implantation rate for the surgical removal group vs . 12% in the direct-to-IVF group, and 14.9% pregnancy rate in the surgical removal group vs . 24.9% in the direct-to-IVF group. Damage to ovarian reserve and function due to surgery is exacerbated by large cyst size, stripping of the pseudocapsule and older age. Larger endometrioma, ablation of the endometrioma base and younger age are associated with higher recurrence rate. Conclusion: The patient’s age, in addition to the size and type of endometrioma, can direct and indicate the timing of surgical management. Bilateral endometriomas and those larger than 7 cm are associated with more damage to ovarian reserve due to disease and surgery, as compared with unilateral lesions and those smaller than 7 cm. High-risk adolescents and very young women seeking fertility treatment can thus benefit from an early diagnosis of endometrioma. Treatment by trans vaginal hydro-laparoscopy of selected cases can probably be suggested for the treatment of small endometriomas, since 5fr instruments are used following microsurgery principles. Therefore, an early diagnosis of endometrioma, especially in young patients, must be encouraged, improved and standardized, through stepwise clinical reasoning and diagnostic testing.

Regret over the delay in childbearing decision negatively associates with life satisfaction among Japanese women and men seeking fertility treatment: a cross-sectional study

BackgroundCurrently, in developed countries, increasing numbers of women and men are delaying childbearing but begin seeking fertility treatment later in life. Some women undergoing infertility treatment develop negative feelings such as depression associated with low life satisfaction and regret over the delay in childbearing. We therefore examine the association of life satisfaction with regret over the delay in childbearing decision and infertility-related factors among Japanese women and men seeking fertility treatment.MethodsThis cross-sectional study included 253 women and 196 men referred to fertility facilities in Japan from July to December 2018. Participants completed a questionnaire on life satisfaction, regret over the delay in childbearing decision, infertility-related factors and sociodemographic characteristics. Life satisfaction was measured using the Satisfaction with Life Scale (SWLS), and the degree of regret over delay in childbearing decision was measured on a 7-point Likert scale. Multiple linear regressions, conducted separately by sex, were used to analyze the association of life satisfaction with regret over the delay in childbearing decision and infertility-related factors.ResultsOf the 253 women and 196 men, 102 (40.3%) women and 43 (21.9%) men answered “strongly agree” regarding their regret over the delay in childbearing decision. Among women, life satisfaction was negatively associated with regret (β = − 0.155, 95% CI [− 0.938, − 0.093], p = 0.017), use of assisted reproduction technology (ART) (β = − 0.135, 95% CI [− 2.977, − 0.020], p = 0.047). In contrast, previous live birth was positively associated with life satisfaction (β = 0.134, 95% CI [0.122, 3.739], p = 0.037). In men, we found no significant association of life satisfaction with regret over the delay in childbearing decision and infertility-related factors.ConclusionsRegret over the delay in childbearing decision is negatively associated with life satisfaction among Japanese women seeking fertility treatment. It may be important for women to make better informed decision regarding the timing of childbearing to not regret later in life. Health professionals should address regret over the delay in childbearing decision during fertility treatment and explore ways to spread information on fertility awareness.

Urinary Concentrations of Phthalate Metabolite Mixtures in Relation to Serum Biomarkers of Thyroid Function and Autoimmunity among Women from a Fertility Center.

Background:Although previous epidemiological studies have explored associations of phthalate metabolites with thyroid function, no studies to date have assessed associations of mixtures with thyroid function and autoimmunity among potentially susceptible subgroups such as subfertile women.Objective:We aimed to explore associations of mixtures of urinary phthalate metabolites with serum markers of thyroid function and autoimmunity.Methods:This cross-sectional study included 558 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2005–2015). We quantified urinary concentrations of eight phthalate metabolites using mass spectrometry, and biomarkers of thyroid function [thyroid-stimulating hormone (TSH), free and total thyroxine (, ) and triiodothyronine (, ), and autoimmunity [thyroid peroxidase and thyroglobulin antibodies (TPOAb and TgAb, respectively)] in serum using electrochemiluminescence assays. We applied principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) to identify the main patterns of urinary phthalate metabolites. We used linear mixed models to assess the association between PCA-derived factor scores in quintiles and serum thyroid function and autoimmunity, adjusting for age, body mass index (BMI), specific gravity (SG), and, for the PCA, other factor scores.Results:We observed two factors using PCA, one representing the di(2-ethylhexyl) (DEHP) and another non-DEHP metabolites. Compared to women in the lowest quintile of the DEHP factor scores, women in the highest quintile had significantly lower serum concentrations of , , , and [absolute difference: ; 95% confidence interval (CI): , ; ; absolute difference: ; 95% CI: , ; ; absolute difference: ; 95% CI: 0.54, ; ; and absolute difference: ; 95% CI: , ; , respectively]. Using BKMR, we observed that mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was the primary contributor to these negative associations. DEHP and non-DEHP factor scores were not associated with serum TSH, TgAb, or TPOAb.Conclusions:Mixtures of urinary DEHP metabolites were inversely associated with serum biomarkers of thyroid function but not with autoimmunity, which were within normal ranges for healthy adult women. https://doi.org/10.1289/EHP6740

Phospholipase C zeta profiles are indicative of optimal sperm parameters and fertilisation success in patients undergoing fertility treatment.

Oocyte activation is driven by intracellular calcium (Ca2+ ) oscillations induced by sperm-specific PLCζ, abrogation of which causes oocyte activation deficiency in humans. Clinical PLCζ investigations have been limited to severe male infertility conditions, while PLCζ levels and localisation patterns have yet to be associated with general sperm viability. PLCζ profiles were examined within a general population of males attending a fertility clinic (65 patients; aged 29-53), examining PLCζ throughout various fractions of sperm viability. Male recruitment criteria required a minimum sperm count of 5×106 spermatozoa/mL, while all female patients included in this study yielded at least five oocytes for treatment. Sperm count, motility and semen volume were recorded according to standard WHO reference guidelines and correlated with PLCζ profiles examined via immunoblotting and immunofluorescence. Appropriate fertility treatments were performed following routine clinical standard operating protocols, and fertilisation success determined by successful observation of second polar body extrusion. Four distinct PLCζ patterns were observed at the equatorial, acrosomal+equatorial regions of the sperm head, alongside a dispersed pattern, and a population of spermatozoa without any PLCζ. Acrosomal+equatorial PLCζ correlated most to sperm health, while dispersed PLCζ correlated to decreased sperm viability. Total levels of PLCζ exhibited significant correlations with sperm parameters. PLCζ variance corresponded to reduced sperm health, potentially underlying cases of male sub-fertility and increasing male age. Finally, significantly higher levels of PLCζ were exhibited by cases of fertilisation success, alongside higher proportions of Ac+Eq, and lower levels of dispersed PLCζ. PLCζ potentially represents a biomarker of sperm health, and fertilisation capacity in general cases of patients seeking fertility treatment, and not just cases of repeated fertilisation. Further focused investigations are required with larger cohorts to examine the full clinical potential of PLCζ.

Associations of bedtime, sleep duration, and sleep quality with semen quality in males seeking fertility treatment: a preliminary study

BackgroundPoor sleep has been linked to a number of adverse health outcomes. Recent studies suggest that late bedtimes, short or long sleep durations, and poor sleep quality may impair semen quality. No study has previously explored all three factors in relation to semen quality.ResultsOne hundred and four men and their partners treated at three fertility clinics in Denmark between 2010 and 2012 completed an online-version of the Pittsburgh Sleep Quality Index (PSQI). The results of the semen analyses conducted at the fertility clinics were self-reported and categorised as normal or reduced.Early bedtime (< 10:30 PM) was more often associated with normal semen quality compared with both regular (10:30 PM-11:29 PM) and late (≥11:30 PM) bedtime (OR: 2.75, 95%CI: 1.1–7.1, p = 0.04 and OR: 3.97, 95%CI: 1.2–13.5, p = 0.03). Conventional sleep duration (7.5–7.99 h) was more often associated with normal semen quality than both short (7.0–7.49 h) and very short (< 7.0 h) sleep duration (OR: 1.36, 95% CI: 1.2–12.9, p = 0.03 and OR: 6.18, 95%CI: 1.6–24.2, p = 0.01). Although poor sleep quality was associated with reduced semen quality in the descriptive statistics (p = 0.04), no differences were found between optimal (PSQI ≤6) and either borderline (PSQI 7–8) or poor (PSQI ≥9) sleep quality (OR: 1.19, 95%CI: 0.4–3.4, p = 0.75 and OR: 2.43, 95%CI: 0.8–7.1, p = 0.11) in multivariate regression models.ConclusionEarly bedtimes (< 10:30 PM) and conventional sleep duration (7.5–7.99 h) were associated with self-reported normal semen quality. The role of subjective sleep quality remains uncertain.