A cohort of 1,052 persons (504 men and 548 women) born in 1936 and residing in the Glostrup area, Denmark, underwent a comprehensive physical examination in 1976 at age 40 years, and 966 underwent a complete reexamination five years later. The examinations included blood lead concentration and blood pressure assessment under careful quality control. Complete blood lead and blood pressure data were available for 861 of these subjects (451 men and 410 women). The median blood lead levels were 13 and 9 micrograms/100 ml at age 40 years and 9 and 6 micrograms/100 ml at age 45 years in men and women, respectively. A slightly increased blood lead concentration was seen at age 40 years in women with a systolic blood pressure above 140 mmHg and/or a diastolic blood pressure above 90 mmHg. Systolic blood pressure in men and women and diastolic blood pressure in women correlated significantly with log blood lead at age 40 years but not at age 45 years, a doubling in blood lead being associated with an increase in blood pressure of 3 mmHg or less. Of nine potential confounders assessed, only blood hemoglobin and alleged alcohol intake were significantly associated with both blood lead and blood pressure. If one or both confounders were entered into a multiple regression analysis, all associations between blood lead and blood pressure became nonsignificant, in some cases with a negative regression coefficient. In addition, the blood lead:hemoglobin ratio was poorly associated with blood pressure, particularly in individuals with a low alcohol intake. Because both hemoglobin level and alcohol intake appear to be biologically plausible confounders, any independent effect of low-level lead exposure on blood pressure could not be determined.

STUDY QUESTION Does an individualized serum anti-Müllerian hormone (AMH) based FSH dosing algorithm used in a GnRH antagonist protocol increase the proportion of patients with an intended number of oocytes (5–14) retrieved compared with a standard regimen? SUMMARY ANSWER The AMH-based individualized algorithm did not increase the proportion of patients with an intended oocyte retrieval. WHAT IS KNOWN ALREADY Individualizing treatment for ovarian stimulation by serum AMH or antral follicle count can theoretically improve the ratio between benefits and risks. Current data suggest that there may be a reduced risk of ovarian hyperstimulation syndrome (OHSS), but without improved pregnancy or live birth rates. Only two randomized controlled trials (RCTs) have examined the potential of AMH-based algorithms to optimize the FSH dosing in ovarian stimulation. STUDY DESIGN, SIZE, DURATION A dual-center open-label investigator-driven RCT was conducted between January 2013 and November 2016. Eligibility was assessed in 269 women and 221 were randomized 2:1 between individualized and standard dosing groups. Women with pretreatment serum AMH > 24 pmol/L had 100 IU/day of recombinant FSH (rFSH); AMH 12–24 pmol/L had 150 IU/day of rFSH, and AMH < 12 pmol/L had maximal stimulation with corifollitropin 100 or 150 mg depending on bodyweight ±60 kg. The standard group had 150 IU/day of rFSH irrespective of pretreatment AMH. All patients followed the GnRH-antagonist protocol. The sample size calculation assumed that individualized dosing by AMH would reduce the proportion of unintended oocyte yield (outside the 5–14 range) by 50%, from 35 to 17.5%. In a 2:1 randomization this required 216 patients: 144 in the individualized and 72 patients in the standard group (80% power, 5% significance). PARTICIPANTS/MATERIALS, SETTING, METHODS All women had a presumed ovulatory normal menstrual cycle, were aged 25–38 years, weighed < 75 kg, had pretreatment AMH 4–40 pmol/L, did their first IVF or ICSI cycle and had two ovaries accessible to oocyte retrieval. Recruitment was conducted from both participating sites. Women were excluded if diagnosed with anovulatory polycystic ovary syndrome, endometriosis grade III/IV, hydrosalpings on ultrasound, recurrent miscarriages (≥3), FSH > 12 IU/L or major medical disorders. MAIN RESULTS AND THE ROLE OF CHANCE After randomization 149 women were allocated to the individualized group and 72 to the standard group. The primary outcome of women with an intended (5–14) number of oocytes retrieved was similar in the individualized ( n = 105) versus the standard ( n = 55) rFSH treatment group (72% [95% CI 64–79%] versus 78% [95% CI 67–86%], respectively, P = 0.68, between group standardized mean difference (SMD) −6%, 95% CI: −19–8%). In the hig...