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PurposeTo investigate if breast cancer stage and grade affect fertility preservation outcomes.MethodsWe performed a retrospective cohort study that included premenopausal women with breast cancer undergoing fertility preservation diagnosed between January 2011 and January 2019. The primary outcome measure was the number of mature oocytes (MII) per antral follicle count (AFC). Secondary outcome measures included total oocytes retrieved, total mature oocytes retrieved, and greater than 10 mature oocytes preserved. Univariate and multivariate models were used to assess the association of low vs. high stage (low stage I-II and high stage III-IV) and grade I vs. grade II/III with each outcome, with adjustment for confounders.ResultsA total of 267 premenopausal breast cancer patients undergoing fertility preservation were included in our study, with the majority presenting with low stage (N = 215, 80.5%), grade II/III (N = 235, 88.1%) disease. Baseline AFC, total gonadotropin dose, days of stimulation, and follicles [Formula: see text] 13 mm on the day of trigger did not differ by stage or grade. After adjusting for age, BMI, and baseline AFC, we found that the mean MII per AFC did not differ by stage (1.0 vs. 1.1, P = 0.3) or grade (1.0 vs. 1.0, P = 0.92). Similarly, total oocytes retrieved, total MII retrieved, and percentage of patients who were able to preserve greater than 10 MII did not differ by breast cancer stage or grade (all P > 0.2).ConclusionBreast cancer grade and stage do not impact ovarian stimulation or fertility preservation outcome.

PurposeAs the paradigm shifts towards improving cancer survivorship, an important concern for reproductive-aged women diagnosed with cancer is how their disease and its treatment will affect their future fertility. We sought to characterize pregnancy attempts and outcomes in breast cancer patients following chemotherapy.MethodsWe conducted a prospective cohort study of women diagnosed with breast cancer seen between 2010 and 2019. A questionnaire was administered following cancer treatment with questions regarding oncologic and reproductive history and attempts and method of conception.ResultsOf 181 participants, 46 (25.4%) attempted to conceive following chemotherapy. Thirty-five patients (76.1%) had return of ovarian function. Of those, 34 patients (mean age 32.8 years) first attempted to conceive by intercourse, and 22 (64.7%) became pregnant, resulting in 17 live births. Of the remaining 12 who did not successfully conceive through intercourse, eight went on to try other methods, resulting in five additional pregnancies and one live birth. Twelve patients (mean age 34.6 years) proceeded directly to ART; of those, eight (66.7%) became pregnant, resulting in six live births.ConclusionIn breast cancer patients with return of ovarian function after chemotherapy, half were able to conceive by intercourse alone. In order to maximize reproductive potential in patients who have return of ovarian function, providers should offer natural conception as a reasonable option prior to the use of cryopreserved tissue. For those who did not attempt to conceive on their own, the use of pre-treatment cryopreserved eggs or embryos had a high likelihood of success.

PurposeModification of the trigger used to induce final oocyte maturation in in vitro fertilization (IVF) is a major strategy used to reduce the risk of ovarian hyperstimulation syndrome (OHSS). A novel trigger composed of 1500 IU of human chorionic gonadotropin (hCG) plus 450 IU of follicle-stimulating hormone (FSH) has been developed to reduce OHSS risk. This study compares outcomes of the novel trigger to conventional triggers used in high-risk OHSS patients undergoing IVF.MethodsIn this retrospective cohort study, IVF cycles at high risk for OHSS based on a serum estradiol > 5000 pg/ml on trigger day conducted between January 2008 and February 2016 were evaluated. Oocyte maturation was induced with the novel trigger (1500 IU hCG plus 450 IU FSH) or a conventional trigger [3300 IU hCG, gonadotropin-releasing hormone agonist (GnRHa) alone, or GnRHa plus 1500 IU hCG]. IVF cycle outcomes were compared. Trigger strategies were examined for associations with OHSS development using logistic regression.ResultsAmong 298 eligible IVF cycles identified, there were no differences in oocyte maturation, fertilization, embryo quality, or pregnancy outcomes among all triggers. After adjusting for serum estradiol level and number of follicles, the novel trigger was associated with lower odds of OHSS symptom development compared to the 3300 IU hCG and GnRHa plus hCG 1500 IU triggers (p = 0.007 and 0.04, respectively).ConclusionsThis study suggests that 1500 IU hCG plus 450 IU FSH may be associated with decreased OHSS symptoms compared to conventional triggers, while producing similar IVF and pregnancy outcomes. More important, this novel trigger may provide a superior alternative in down-regulated cycles and in patients with hypothalamic dysfunction where GnRHa triggers cannot be utilized.

The original version of this article unfortunately contained a mistake. The middle initial of Douglas A. Mata was omitted. The original article has been corrected.

Study questionDoes the interval from delivery to initiation of a subsequent ART treatment cycle impact clinical pregnancy or live birth rates?Summary answerAn interval from delivery to treatment start of <6 months or ≥24 months is associated with decreased likelihood of clinical pregnancy and live birth.What is known alreadyShort interpregnancy intervals are associated with poor obstetric outcomes in the naturally conceiving population prompting birth spacing recommendations of 18-24 months from international organizations. Deferring a subsequent pregnancy attempt means a woman will age in the interval with an attendant decline in her fertility.Study design, size, durationRetrospective analysis of the Society for Assisted Reproductive Technology Clinical Outcome Reporting System (SARTCORS) cohort containing 61 686 ART cycles from 2004 to 2013.Participants/materials, setting, methodsThe delivery-to-cycle interval (DCI) was calculated for patients from SARTCORS with a history of live birth from ART who returned to the same clinic for a first subsequent treatment cycle. Generalized linear models were fit to determine the risk of clinical pregnancy and live birth by DCI with subsequent adjustment for factors associated with outcomes of interest. Predicted probabilities of clinical pregnancy and live birth were generated from each model.Main results and the role of chanceA DCI of <6 months was associated with a 5.6% reduction in probability of clinical pregnancy (40.1 ± 1.9 versus 45.7 ± 0.6%, P = 0.009) and 6.8% reduction in live birth (31.6 ± 1.7 versus 38.4 ± 0.6%, P = 0.001) per cycle start compared to a DCI of 12 to <18 months. A DCI of ≥24 months was associated with a 5.1% reduction in probability of clinical pregnancy (40.6 ± 0.5 versus 45.7 ± 0.6%, P < 0.001) and 5.7% reduction in live birth (32.7 ± 0.5 versus 38.4 ± 0.6%, P < 0.001) compared to 12 to <18 months.Limitations, reasons for cautionThe SART database is reliant upon self-report of man

PurposeAfter chemotherapy for breast cancer, most women will recover some ovarian function, but the timing and extent of this recovery are poorly understood. We studied post-chemotherapy ovarian recovery in women with and without a history of ovarian suppression during chemotherapy.MethodsReproductive age breast cancer patients who were seen prior to chemotherapy for fertility preservation consult were consented for follow-up ovarian function assessment (every 3-6 months after chemotherapy) with antral follicle count (AFC) in this prospective cohort study. We restricted our analysis to those with menses present after chemotherapy. Box plots were used to demonstrate the change in follow-up AFC versus time elapsed after chemotherapy. A mixed effects regression model was used to assess differences in AFC.ResultsEighty-eight patients with a history of newly diagnosed breast cancer were included. Forty-five patients (51%) had ovarian suppression with GnRH agonist (GnRHa) during chemotherapy. AFC recovery appeared to plateau at 1 year after completing chemotherapy at a median of 40% of pre-chemotherapy AFC. After adjustment for age, initial AFC, cyclophosphamide exposure, combined hormonal contraceptive (CHC) use, and tamoxifen use, AFC recovered faster and to a greater degree for those women who underwent GnRHa therapy for ovarian protection during chemotherapy (P = 0.032).ConclusionsWomen with menses after chemotherapy for breast cancer appear to recover their full potential AFC 1 year after their last chemotherapy dose. Treatment with GnRHa during chemotherapy is associated with a higher degree of AFC recovery. The findings of this study can aid in counseling patients prior to chemotherapy about expectations for ovarian recovery and planning post-treatment fertility preservation care to maximize reproductive potential when pre-treatment fertility preservation care is not possible or has limited oocyte yield.

PurposeData have demonstrated an association between regret and lack of fertility counseling among patients undergoing treatment for non-gynecologic cancers. We sought to determine if fertility-related regret is reduced with pre-treatment counseling or fertility-sparing surgery (FSS) in patients with gynecologic cancers.MethodsA cross-sectional survey was administered to 593 reproductive-age survivors (18-40 years old at diagnosis) of localized cervix, ovarian, or endometrial cancers that were eligible for FSS. A validated decision regret score was used to evaluate regret in patients.ResultsFour hundred seventy women completed the survey. Forty-six percent received pre-treatment counseling about treatment's effects on fertility. Having received counseling (adjusted ß-coefficient of -1.24, 95 % CI = -2.29 to -0.18, p = 0.02), satisfactory counseling (adjusted ß-coefficient of -2.71, 95 % CI = -3.86 to -1.57, p < 0.001), and FSS (adjusted ß-coefficient of -1.26, 95 % CI = -2.39 to -0.14, p = 0.03) were associated with lower regret post-treatment, after adjusting for age. Time since diagnosis, prior parity, socioeconomic status and cancer type were not associated with regret (p > 0.05). While 50 % of women reported desiring more children after diagnosis, desire for children after treatment was associated with increased regret (adjusted ß-coefficient of 3.97, 95 % CI = 2.92-5.02, p < 0.001).ConclusionsThough less than half of study participants received counseling about the effect of cancer treatment on future fertility, both fertility counseling and FSS were associated with decreased regret in reproductive-aged women with gynecologic cancers. The desire for more children after treatment was associated with increased regret.Implications for cancer survivorsInquiring about fertility desires and providing counseling regarding reproductive outcomes following cancer treatment should be implemented as part of the treatment process.

PurposeUnlike infertility, patients presenting for fertility preservation (FP) are often using combined hormonal contraceptives (CHC). We studied whether long-term (≥6 months) CHC use is associated with reversible suppression of antral follicle count (AFC).MethodsThis is a longitudinal study of FP cycles from 2012 to 2016. We studied three groups: those without CHC exposure (NO CHC), those with CHC usage with a CHC break (BREAK), and without a break (NO BREAK) prior to ovarian stimulation. We assessed ovarian reserve by AFC at initial consultation and discussed the possibility of CHC suppression of AFC. Patients chose between ovarian stimulation with no CHC break versus ovarian stimulation after a CHC break. AFC was measured serially in the BREAK group. We assessed whether AFC suppression was reversed in the BREAK group. Total oocyte yield was compared among the NO CHC, BREAK, and NO BREAK groups. T tests, ANOVA, and linear/logistic regressions were used.ResultsSeven hundred forty-three women underwent FP. Twenty-one percent (n = 154) were taking long-term CHC (≥6 months). AFC suppression was more likely with CHC use (OR 1.6, 95% CI 1.1-2.4, P = 0.011). The BREAK group (n = 79) stopped CHC for an average of 4 months. AFC improvement started at 1 month and plateaued at approximately 6- to 7-month break. The BREAK group had approximately twice as many oocytes per initial AFC as NO BREAK (2.8 ± 3.8 vs. 1.4 ± 0.9, P < 0.001).ConclusionsWhen women present for FP on CHC, AFC may be suppressed. A CHC break of several months is associated with an increase in AFC and a potential improvement in overall egg yield.

BackgroundOvarian stimulation for assisted reproductive technology (ART) overcomes the physiologic process to develop a single dominant follicle. However, following stimulation, egg recovery rates are not 100%. The objective of this study is to determine if the follicular fluid hormonal environment is associated with oocyte recovery.MethodsThis is a prospective study involving patients undergoing ART by standard ovarian stimulation protocols at an urban academic medical center. A total of 143 follicular fluid aspirates were collected from 80 patients. Concentrations of FSH, hCG, estradiol, progesterone, testosterone and prolactin were determined. A multivariable regression analysis was used to investigate the relationship between the follicular fluid hormones and oocyte recovery.ResultsIntrafollicular FSH was significantly associated with oocyte recovery after adjustment for hCG (Adjusted odds ratio (AOR) = 1.21, 95%CI 1.03-1.42). The hCG concentration alone, in the range tested, did not impact the odds of oocyte recovery (AOR = 0.99, 95%CI 0.93-1.07). Estradiol was significantly associated with oocyte recovery (AOR = 0.98, 95% CI 0.96-0.99). After adjustment for progesterone, the strength of association between FSH and oocyte recovery increased (AOR = 1.84, 95%CI 1.45-2.34).ConclusionThe relationship between FSH and oocyte recovery is significant and appears to work through mechanisms independent of the sex hormones. FSH may be important for the physiologic event of separation of the cumulus-oocyte complex from the follicle wall, thereby influencing oocyte recovery. Current methods for inducing the final stages of oocyte maturation, with hCG administration alone, may not be optimal. Modifications of treatment protocols utilizing additional FSH may enhance oocyte recovery.

BackgroundOvarian stimulation for assisted reproductive technology (ART) overcomes the physiologic process to develop a single dominant follicle. However, following stimulation, egg recovery rates are not 100%. The objective of this study is to determine if the follicular fluid hormonal environment is associated with oocyte recovery.MethodsThis is a prospective study involving patients undergoing ART by standard ovarian stimulation protocols at an urban academic medical center. A total of 143 follicular fluid aspirates were collected from 80 patients. Concentrations of FSH, hCG, estradiol, progesterone, testosterone and prolactin were determined. A multivariable regression analysis was used to investigate the relationship between the follicular fluid hormones and oocyte recovery.ResultsIntrafollicular FSH was significantly associated with oocyte recovery after adjustment for hCG (Adjusted odds ratio (AOR) = 1.21, 95%CI 1.03-1.42). The hCG concentration alone, in the range tested, did not impact the odds of oocyte recovery (AOR = 0.99, 95%CI 0.93-1.07). Estradiol was significantly associated with oocyte recovery (AOR = 0.98, 95% CI 0.96-0.99). After adjustment for progesterone, the strength of association between FSH and oocyte recovery increased (AOR = 1.84, 95%CI 1.45-2.34).ConclusionThe relationship between FSH and oocyte recovery is significant and appears to work through mechanisms independent of the sex hormones. FSH may be important for the physiologic event of separation of the cumulus-oocyte complex from the follicle wall, thereby influencing oocyte recovery. Current methods for inducing the final stages of oocyte maturation, with hCG administration alone, may not be optimal. Modifications of treatment protocols utilizing additional FSH may enhance oocyte recovery.

ObjectiveTo investigate whether delaying the start of ovarian stimulation with GnRH antagonist improves ovarian response in poor responders.DesignRetrospective study.SettingAcademic medical center.Patient(s)Thirty patients, who responded poorly and did not get pregnant with conventional estrogen priming antagonist IVF protocol.Intervention(s)Delayed-start antagonist protocol (estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation).Main outcome measure(s)Number of dominant follicles and mature oocytes retrieved, mature oocyte yield, and fertilization rate.Result(s)The number of patients who met the criteria to proceed to oocyte retrieval was significantly higher in the delayed-start protocol [21/30 (70%)] compared with the previous conventional estrogen priming antagonist cycle [11/30 (36.7%)]. The number of dominant follicles was significantly higher in the delayed-start (4.2 ± 2.7) compared with conventional (2.4 ± 1.3) protocol. In patients who had oocyte retrieval after both protocols (n = 9), the delayed start resulted in shorter ovarian stimulation (9.4 ± 1.4 days vs. 11.1 ± 2.0 days), higher number of mature oocytes retrieved (4.9 ± 2.0 vs. 2.2 ± 1.1), and a trend toward increased fertilization rates with intracytoplasmic sperm injection (ICSI; 86 ± 17% vs. 69 ± 21%) compared with conventional protocol. After delayed start, the average number of embryos transferred was 2.8 ± 1.4 with implantation rate of 9.8% and clinical pregnancy rate of 23.8%.Conclusion(s)The delayed-start protocol improves ovarian response in poor responders by promoting and synchronizing follicle development without impairing oocyte developmental competence.

ObjectiveTo determine whether reproductive age, as indexed by a validated marker of ovarian reserve (antimüllerian hormone [AMH]), varies among women of different race/ethnic backgrounds.DesignCross-sectional study.SettingCommunity-based sample.Patient(s)Multiethnic sample of 947 (277 white, 237 African American, 220 Latina, and 213 Chinese) healthy and regularly cycling premenopausal women, ages 25-45.Intervention(s)None.Main outcome measure(s)AMH level.Result(s)A multivariate model was fit examining race/ethnicity, covariates, nonlinear terms for age (age(2), age(3)), and body mass index (BMI(2), BMI(3)), and two-way interactions between race/ethnicity and each of the other predictor variables in relation to AMH. After backward elimination, significant effects included race/ethnicity (F = 8.45), age (F = 349.94), race/ethnicity-by-linear age interaction (F = 4.67), age(2) (F = 31.61), and BMI (F = 10.69). Inspection of the significant race/ethnicity-by-linear age interaction showed AMH levels were consistently lower among Latina women compared with white women across all ages, whereas AMH levels were lower among African American and Chinese women compared with the white women at younger and middle ages, respectively. The AMH levels were higher among African American compared with Latina and Chinese women at older ages.Conclusion(s)Although the results must be considered preliminary, the findings are twofold: African American women may have lower AMH levels at younger ages but experience less of a reduction in AMH with advancing age, and Latina and Chinese women compared with white women may have lower AMH levels, marking a lower ovarian reserve and a possibly increased risk for earlier menopause.

ObjectiveThe aim of this study was to evaluate the extent to which mild disruptions in ovarian function, indexed by changes in menstrual cycle length, may relate to cardiometabolic and psychological health in premenopausal women.MethodsAmong 804 healthy, regularly cycling women (aged 25-45 y; mean [SD] age, 35.5 [5.5] y), patterns of any change (shortening, lengthening, or increased variability) versus no change in menstrual cycle length were examined in relation to a composite of cardiometabolic risk and individual risk factors (high-density lipoprotein, triglycerides, waist circumference, glucose, and hypertensive status), as well as in relation to depression indicators (Center for Epidemiological Studies Depression Scale score ≥16 [yes/no], lifetime depression diagnosis [yes/no], and lifetime antidepressant medication use [yes/no]). Models were also explored to test whether changes in menstrual cycle length mediated relations between depression history and cardiometabolic risk.ResultsIn covariate-adjusted models compared with no change, any change in menstrual cycle length was associated with higher cardiometabolic risk composite scores and lower high-density lipoprotein (P < 0.05). In addition, compared with no change, any change in menstrual cycle length was associated with a Center for Epidemiological Studies Depression Scale score of 16 or higher, having received a depression diagnosis, and having used antidepressant medications (P < 0.05). In exploratory analyses, any change in menstrual cycle length partially mediated the relation between depression history and cardiometabolic risk (b = 0.152, P = 0.040), which attenuated (b = 0.129, P = 0.083) when any change in menstrual cycle length was covaried.ConclusionsFindings suggest that disruptions in ovarian function, marked by subtle changes in menstrual cycle length, may relate to aspects of cardiometabolic and psychological health among healthy, premenopausal women.

ObjectiveThe menopausal transition is associated with an increase in risk for cardiovascular disease; however, whether variability in reproductive aging relates to cardiovascular risk factors in the premenopausal period has not been studied.MethodsIn a multiethnic sample of 951 healthy, regularly cycling women aged 25 to 45 years (mean [SD] age, 35.2 [5.5] y), we examined antimüllerian hormone (AMH), a validated marker of ovarian reserve, in relation to the overall number of cardiometabolic risk factors, calculated as the sum of the five components of metabolic syndrome (triglycerides ≥150 mg/dL; high-density lipoprotein <50 mg/dL; homeostasis model assessment of insulin resistance ≥2.6; waist circumference equal to or higher than race-specific cutoff; and hypertensive [vs normotensive] status), and in relation to each of these risk factors individually.ResultsIn age-adjusted models, results showed that the number of cardiometabolic risk factors was 52.1% higher among women with low versus high AMH levels and 46.0% higher among women with mid versus high AMH levels. In addition, results showed that low and mid levels of AMH (vs high) were associated with an increase in risk with respect to high-density lipoprotein (odds ratio [OR], 1.814; 95% CI, 1.211-2.718 and OR, 1.568; 95% CI, 1.083-2.269, respectively), waist circumference (OR, 2.012; 95% CI, 1.380-2.934 and OR, 1.881; 95% CI, 1.333-2.654, respectively), and hypertensive status (OR, 2.373; 95% CI, 1.095-5.143 and OR, 2.052; 95% CI, 0.976-4.314, respectively) outcomes. Associations, however, attenuated when body mass index was covaried (Ps > 0.05).ConclusionsCross-sectional evidence suggests that having a greater ovarian reserve is associated with having a healthier cardiometabolic risk factor profile. Future longitudinal studies are needed to determine whether this association may be mediated by body mass index.

BackgroundThe ovarian reserve (number and quality of oocytes) is correlated with reproductive potential as well as somatic health, and is likely to have multiple genetic and environmental determinants. Several reproductive hormones are closely linked with the oocyte pool and thus can serve as surrogate markers of ovarian reserve. However, we know little about the underlying genes or genetic variants.MethodsWe analyzed genetic variants across the genome associated with two hormonal markers of ovarian reserve, FSH and anti-Mullerian hormone, in a reproductively normal population of Caucasian (n = 232) and African American (n = 200) women, aged 25-45 years. We also examined the effects of environmental or lifestyle factors on ovarian reserve phenotypes.ResultsWe identified one variant approaching genome-wide significance (rs6543833; P= 8.07 × 10⁻⁸) and several nominal variants nearby and within the myeloid-associated differentiation marker-like (MYADML) gene, that were associated with FSH levels in African American women; these were validated in Caucasian women. We also discovered effects of smoking and oral contraceptive use on ovarian reserve phenotypes, with alterations in several reproductive hormones.ConclusionsThis work is the largest study on ovarian reserve in women of reproductive age and is the only genome-wide study on ovarian reserve markers. The genes containing or near the identified variants have no known roles in ovarian biology and represent interesting candidate genes for future investigations. The discovery of genetic markers may lead to better long-range predictions of declining ovarian function, with implications for reproductive and somatic health.

BackgroundThe ovarian reserve (number and quality of oocytes) is correlated with reproductive potential as well as somatic health, and is likely to have multiple genetic and environmental determinants. Several reproductive hormones are closely linked with the oocyte pool and thus can serve as surrogate markers of ovarian reserve. However, we know little about the underlying genes or genetic variants.MethodsWe analyzed genetic variants across the genome associated with two hormonal markers of ovarian reserve, FSH and anti-Mullerian hormone, in a reproductively normal population of Caucasian (n = 232) and African American (n = 200) women, aged 25-45 years. We also examined the effects of environmental or lifestyle factors on ovarian reserve phenotypes.ResultsWe identified one variant approaching genome-wide significance (rs6543833; P= 8.07 × 10⁻⁸) and several nominal variants nearby and within the myeloid-associated differentiation marker-like (MYADML) gene, that were associated with FSH levels in African American women; these were validated in Caucasian women. We also discovered effects of smoking and oral contraceptive use on ovarian reserve phenotypes, with alterations in several reproductive hormones.ConclusionsThis work is the largest study on ovarian reserve in women of reproductive age and is the only genome-wide study on ovarian reserve markers. The genes containing or near the identified variants have no known roles in ovarian biology and represent interesting candidate genes for future investigations. The discovery of genetic markers may lead to better long-range predictions of declining ovarian function, with implications for reproductive and somatic health.

ObjectiveThe aim of this study was to examine psychological factors in relation to antral follicle count (AFC), a marker of ovarian reserve, in a multiethnic sample of 683 premenopausal women in the Ovarian Aging (OVA) Study.MethodsIn cross-sectional analyses, linear regression was performed to determine whether AFC decline across women varied over levels of depression as well as depression in combination with psychological stress. The total and subscale scores of the Center for Epidemiological Studies Depression Scale were used to measure depression, and the Perceived Stress Scale was used to measure psychological stress.ResultsAfter covariate adjustment, the two-way interaction of age × positive affect and the three-way interaction of age × positive affect × stress were related to AFC (b = 0.047, P = 0.036; b = 0.012, P = 0.099, respectively). In stratified analyses, stress was related to AFC in women with low positive affect (b = -0.070, P = 0.021) but not in women with high positive affect (b = 0.018, P = 0.54). AFC decline across women was progressively higher in women with low positive affect who reported low (-0.747 follicles/year), mid (-0.920 follicles/year), and high (-1.112 follicles/year) levels of stress. Results examining the Center for Epidemiological Studies Depression Scale total and remaining subscale scores were all nonsignificant (P values > 0.05).ConclusionsCross-sectional evidence suggests that (1) women with low positive affect may experience accelerated AFC decline and (2) low positive affect may be a vulnerability factor, or, alternatively, high positive affect may be a protective factor, in moderating the negative effects of psychological stress on AFC decline.