Does pregnancy induce the shedding of premalignant ovarian cells?

BACKGROUND: High parity is associated with reduced risk of ovarian cancer. One hypothesis is that pregnancy is associated with clearance of a fraction of the genetically modified (premalignant) cells from the ovaries. METHODS: We evaluated this hypothesis using a model that estimates the cell clearance fraction at first and second pregnancy according to age at pregnancy. The model was fitted using reproductive history data from a cohort of 1.5 million Danish women born between 1935 and 1978 and followed for 28.7 million person-years. During this follow-up period, 2,035 developed invasive ovarian cancer. RESULTS: We found the model to have a satisfactory fit despite the very few parameters involved. The model estimated similar cell clearance fractions for the first and second pregnancy and decreasing clearance with later age at pregnancy. CONCLUSION: The relation of pregnancy history to risk of ovarian cancer can be well described by a cell clearance model that allows the cell clearance fraction to decrease with age at pregnancy.     

Does size matter in females? An overview of the impact of the high variation in the ovarian reserve on ovarian function and fertility, utility of anti-Müllerian hormone as a diagnostic marker for fertility and causes of variation in the ovarian reserve in cattle

The mechanism whereby the inherently high variation in ovary size and the total number of high-quality oocytes in ovaries (ovarian reserve) impact on ovarian function and fertility, diagnostics to measure the size of the ovarian reserve and the factors that cause variation in the ovarian reserve are unknown. Our results show that cattle can be phenotyped reliably based on the number of antral follicles growing during follicular waves (antral follicle count, AFC). Young adult cattle with a consistently low v. a high AFC have smaller gonads, a markedly diminished ovarian reserve and many other phenotypic characteristics usually associated with ovarian aging and infertility. A powerful new approach based on a single measurement of serum concentration of anti-Müllerian hormone (AMH) is described to test the longstanding hypothesis that the size of the ovarian reserve is positively associated with fertility. Also, new evidence shows that maternal environment has a critical role in regulation of the high variation in the ovarian reserve and perhaps fertility in offspring. These results support the conclusion that the inherently high variation in the ovarian reserve, potentially caused by alterations in the maternal environment, has a negative impact on ovarian function that may result in suboptimal fertility in young adult cattle, and a single AMH measurement can be used reliably in future studies to determine if fertility is suboptimal in young adult cattle with low circulating AMH concentrations and a correspondingly diminished ovarian reserve.     

Longitudinal assessment of anti-Müllerian hormone after cesarean section and influence of bilateral salpingectomy on ovarian reserve

ObjectiveThis study aimed to compare longitudinal changes in ovarian reserve markers after cesarean section (CS) with and without bilateral salpingectomy (BS).Study designWe prospectively enrolled women >35 weeks’ gestation scheduled for CS alone or CS + BS and obtained blood samples for anti-Müllerian hormone prior to surgery and at 3 and 6 months after surgery. At the 3-month visit, we similarly performed transvaginal ultrasound for antral follicle count.ResultsWe enrolled 50 women; 30 underwent CS only and 20 underwent CS + BS. Although anti-Müllerian hormone level increased over 6 months of follow-up in both groups, no clinically important differences in the geometric mean (interquartile range) (ng/mL) were observed at any timepoint (baseline [0.69 {0.36?1.21} {CS only} vs 0.49 {0.32?2.10} {CS + BS}, p = 0.64]; 3 months [1.35 {0.58?3.13} vs 1.45 {1.04?2.25}, p = 0.79]; and 6 months [1.74 {0.93?4.45} vs 2.60 {1.41?5.10}, p =0.27]). Similarly, we detected no difference in antral follicle count.ConclusionBS at the time of CS does not have a negative impact on ovarian reserve 6 months after surgery.ImplicationWhile our results provide reassuring data that bilateral salpingectomy for permanent contraception at the time of cesarean section does not impact ovarian reserve, longer adequately powered studies are needed.     

Assessment of transposed ovarian movement: how much of a safety margin should be added during pelvic radiotherapy?

The purpose of this study was to analyze transposed ovarian movement. Data from 27 patients who underwent ovarian transposition after surgical treatment for uterine cancer were retrospectively analyzed. Computed tomography (CT) images including transposed ovaries were superimposed on other CT images acquired at different times, and were matched on bony structures. Differences in ovarian position between the CT images were measured. The planning organ at risk volume (PRV) margins were calculated from the formula of the 90% reference intervals (RIs) and the 95% RI, which were defined as mean ± 1.65 standard deviation (SD) and mean ± 1.96 SD, respectively. The 90% RI in the cranial, caudal, anterior, posterior, left and right directions were 1.5, 1.5, 1.4, 1.0, 1.7 and 0.9 cm, respectively. The 95% RI in the corresponding directions were 1.5, 2.0, 1.7, 1.2, 1.9 and 1.2 cm, respectively. These data suggest that bilateral ovaries need a PRV margin of ∼2 cm in all directions. The present study suggests that a transposed ovary needs the same PRV margin as a normal ovary (∼2 cm). Even after transposition, ovaries should be kept away from the radiation field to take into consideration the degree of ovarian movement.     

Quality of life in female cancer survivors: is it related to ovarian reserve?

Purpose

The purpose of the study is to assess the quality-of-life scores and possible association with measures of ovarian reserve in female cancer survivors compared to healthy controls of similar age.

Methods

In this prospective cohort study, fifty-nine cancer survivors aged 16–39 years and 66 healthy, similarly aged unexposed women were recruited at the University of Pennsylvania. The primary outcome measures are the generic and cancer-specific domain scores on the Quality of Life in Adult Cancer Survivors (QLACS) instrument, early follicular phase serum hormones, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), inhibin B (INH), anti-Mullerian hormone (AMH), and ovarian ultrasound measurements [ovarian volume and antral follicle count (AFC)].

Results

Cancer survivors had significantly higher total and cancer-specific domain scores compared to unexposed participants. Serum AMH, INH, ovarian volume, and AFC were lower while serum FSH was higher in cancer survivors. Although survivors exhibited diminished ovarian reserve, these markers were not independently associated with total QLACS score. Cancer survivors with irregular menstrual function were found to have lower quality-of-life (QOL) scores than those with regular cycles.

Conclusions

We found that QOL appears to be significantly impaired in cancer survivors compared to controls, even when remote from initial cancer diagnosis. In addition, our study suggests that reproductive aging contributes to QOL in the setting of irregular menses and likely profound impairment of ovarian function.     

Is tubal sterilization associated with an increased risk of subsequent hysterectomy but a decreased risk of ovarian cancer? A review of recent literature

Recent epidemiologic studies have suggested that tubal sterilization (TS) may lead to an increased incidence of subsequent hysterectomy but a decreased risk of ovarian cancer. This review evaluates the nature and magnitude of these two relationships, which should be of great concern and interest to women, clinicians and the administrators of family planning programs.The positive relationship between TS and subsequent hysterectomy is more likely to be of a motivational rather than biological nature, and a considerable number of unnecessary hysterectomies after TS could be avoided by changing the attitudes of physicians and women.The inverse relationship between TS and ovarian cancer appears causal, although the exact biological mechanisms remain to be clarified. Theoretically, this non-contraceptive beneficial effect of TS could be used as a primary preventive measure to curb the incidence of the highly fatal ovarian cancer. However, a number of medical, ethical, and economic questions attending use of a generally irreversible contraceptive procedure as a preventive measure must first be answered.The issue of whether TS is associated with any long-term sequelae, and, if so, whether the association is of a cause-and-effect nature or a by-product of time passage and aging of the woman, should be addressed by well-designed studies.

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Resumen Recientes estudios epidemiológicos han sugerido que la esterilización tubárica (ET) podrá ocasionar una mayor incidencia de histerectomías posteriores pero un menor riesgo de cáncer ovárico. Este examen evalúa la naturaleza y magnitud de estas dos relaciones, que interesan y preocupan mucho a las mujeres, los médicos clínicos y los administradores de programas de planificación familiar.Es probable que la relación positiva entre la ET y la histerectomía posterior sea de naturaleza más bien motivacional que biológica, y se pordría evitar un número considerable de histerectomías innecesarias después de la ET cambiando las actitudes de los médicos y de las mujeres.La relación inversa entre la ET y el cáncer ovárico parece causal, si bien los mecanismos biológicos exactos no han sido aún aclarados. Teóricamente, este efecto benéfico no anticonceptivo de la ET podría utilizarse como medida preventiva primaria para reducir la incidencia del cáncer ovárico, de tan alta mortalidad. Sin embargo, primero debe responderse a una serie de preguntas de tipo médico, ético y económico relativas al uso de un procedimiento anticonceptivo generalmente irreversible como medida preventiva.La cuestión de si la ET está asociada con alguna secuela a largo plazo y, de ser así, si tal asociación es de naturaleza causa y efecto o un subproducto del transcurso del tiempo y del envejecimiento de la mujer debe ser examinada mediante estudios bien diseñados

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Resumé De récentes études épidémiologiques laissent à penser que la stérilisation tubaire (ST) peut entraîner une augmentation des cas d'hystérectomie ultérieure mais une diminution des cas de cancer ovarien. La présente étude passe en revue la nature et l'ordre de grandeur de ces deux relations, qui devraient représenter, pour les femmes, les cliniciens et les administrateurs des programmes de planning familial, un sujet de préoccupation et d'intérêt.La relation positive entre la ST et une hystérectomie ultérieure relève sans doute plus d'une question de motivation que du domaine biologique, et un nombre considérable d'hystérectomies inutiles après la ST pourrait être évité si l'on changeait les atttudes des médecins et des femmes.A l'inverse, la relation entre la ST et le cancer ovarien semble être causale, bien que ses mécanismes biologiques précis soient à élucider. En théorie, cet avantage non contraceptif de la ST pourrait être mis à profit comme mesure préventive primaire contre l'incidence du cancer de l'ovaire, le plus souvent mortel. Toutefois, il faudra d'abord trouver la réponse à un certain nombre de questions d'ordre médical, éthique et économique que pose une intervention contraceptive généralement irréversible en tant que mesure de prévention.Des études bien conçues devraient examiner la question de savoir si la TS est associée à des séquelles à long terme et, dans l'affirmative, si cette association est une relation de cause à effect ou produite par le passage du temps et le vieillissement de la femme.

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This paper was prepared while the author was associated with Family Health International, PO Box 13950, Research Triangle Park, NC 27709, USA     

Live birth after transplantation of cryopreserved ovarian tissue with two-year follow-tup: Report of the first Chinese case北大核心CSCD

Objective To investigate the safety and efficacy of in vitro activation (IVA) following cryopreserved ovarian tissue autotransplantation in the treatment of patients with premature ovarian insufficiency (POI). Methods We reported and reviewed the treatment and follow-up of a patient with POI, who underwent IVA combined with cryopreserved ovarian tissue transplantation. Results The patient naturally concepted and delivered a healthy baby boy, who became the first live birth after cryopreserved ovarian tissue transplantation in China. The baby showed normal physical, motor and mental development during two-year follow-up. Conclusion IVA combined with cryopreserved ovarian tissue transplantation can effectively activate residual follicles in some POI patients and allow them to conceive their own genetic offspring. IVA technology may become a new choice for fertility treatment of POI patients. © 2020 Chinese Medical Journals Publishing House Co.Ltd. All Rights Reserved.     

Habitual physical activity reduces risk of ovarian cancer: A case–control study in southern China

ObjectiveTo ascertain the relationship between habitual physical activity and the risk of ovarian cancer among southern Chinese women.MethodA case–control study was conducted in Guangzhou, Guangdong Province, during 2006–2008. Information on physical activity exposure and lifestyle characteristics was obtained from 500 incident ovarian cancer patients and 500 hospital-based controls (mean age 59 years) using a validated and reliable questionnaire. Logistic regression analyses were performed to assess the association between physical activity levels and the ovarian cancer risk.ResultsThe control subjects reported significantly longer duration of strenuous sports and moderate activity in daily life than the ovarian cancer patients. Increased engagements in such leisure time activities were associated with reduced cancer risks after adjustment for confounding factors. A significant inverse dose–response relationship was also found for total physical activity exposure, with adjusted odds ratio 0.49 (95% confidence interval 0.35–0.68) for women engaged in 23 or more metabolic equivalent tasks (MET)-hours per week relative to those less than 12 MET-hours per week.ConclusionThe study provided evidence of an inverse association between habitual physical activity and the risk of ovarian cancer, which is important for the promotion and encouragement of leisure time exercise activities to prevent the disease.     

Psychosocial counseling after diagnosis for non-carriers of hereditary breast cancer or ovarian cancer; is it needed?

In 4 women, aged 29, 44, 51 and 63 years, from families with hereditary breast and ovarian cancer (BRCA1 and BRCA2), DNA testing had shown that they were non-carriers of a genetic mutation. They were invited for a study of what this finding meant to them. Two of them had no problems and 2 experienced psychological problems such as guilt feelings and distress from changed future perspectives. Psychosocial care was offered. One woman first accepted the psychosocial care, but later refused, because talking provoked painful memories. One woman got psychosocial care in the region where she lived. To select women with distress who need psychosocial care after being identified as non-carriers, the counsellor could ask after deaths in the family, the kind of contact in the family, complaints of gloominess or worrying, and previous psychosocial therapy.     

A randomized study of the effect of mifepristone alone or in conjunction with ethinyl estradiol on ovarian function in women using the etonogestrel-releasing subdermal implant, Implanon®

BackgroundMifepristone alone or in combination with ethinyl estradiol (EE) can effectively stop an episode of uterine bleeding in women using the etonogestrel-releasing contraceptive implant, Implanon® but could impair contraceptive efficacy.AimTo examine the effects of administration of mifepristone alone or with EE on ovarian function and cervical mucus consistency in women using Implanon.Study DesignWomen using Implanon were randomized to mifepristone 25 mg twice daily on day 1 plus placebo 1 daily for 4 days or plus EE 20 mcg daily for days 2–5. Measurements of serum estradiol (E₂), progesterone (P₄), luteinizing hormone (LH), follicle-stimulating hormone (FSH), cervical mucus examination and maximal follicle size (by vaginal ultrasound) were carried out at various times.ResultsFollowing mifepristone intake, there was a dramatic increase in E₂ levels ranging from 543 to 1183 pmol/L (p=.000), which was not correlated with maximal follicle size or preceded by LH or FSH increase. The increase in E₂ triggered an LH increase resulting in development of a luteinized follicle in four women with no evidence of ovulation. One of these women had estradiol and progesterone levels suggestive of ovulation, but no corpus luteum was seen. Almost all women had very low mucus scores, which did not correlate with E₂ levels.DiscussionDespite a transient increase in E₂ levels after mifepristone, there was no evidence of subsequent ovulation irrespective of whether they also received EE. The mechanism by which mifepristone in the presence of etonogestrel results in a rapid increase in E₂ levels remains unclear and could not be related to any significant changes in FSH, LH, ovarian follicle dynamics or subsequent possible ovulation.ConclusionPregnancy is very unlikely to occur if mifepristone and EE are given during use of Implanon to stop an episode of bleeding.     

Analysis of relative factors and prediction model for optimal ovarian response in patients with follicular phase long-acting long protocol北大核心CSCD

Objective To explore the relative factors for best ovarian response in patients undergoing assisted reproductive technology with follicular phase long-acting long protocol, and to establish a Nomogram prediction model of ovarian response. Methods This retrospective cohort study analyzed the clinical data of 1289 patients who received assisted reproductive treatment in the Center for Reproductive Medicine of Fujian Maternity and Child Health Hospital from July 1, 2018 to July 30, 2019. According to the number of oocytes retrieved, there were 164 cases in the low ovarian response group (≤5 oocytes retrieved), 891 cases in the normal ovarian response group (the number of retrieved oocytes was >5, and ≤18), and 234 cases in the high ovarian response group (>18 oocytes retrieved). Independent factors affecting ovarian reactivity were screened by logistic regression, which were the model entry variables, and a Nomogram prediction model was established based on the regression coefficients in the model. Results There were statistically significant differences in age, anti-Müllerian hormone (AMH) level and antral follicle count (AFC) among the three groups [32.43±3.99, 31.48±3.89, 29.91±3.73; (2.53±1.90) μg/L, (3.79±2.20) μg/L, (5.94±3.12) μg/L; 10.24±3.10, 14.50±3.29, 19.81±3.44; all P<0.001]. There were no significant differences in body mass index (BMI), duration of infertility and causes of tubal infertility (all P> 0.05). The initial dosage of gonadotropin (Gn) used for ovarian hyperstimulation among the three groups was statistically different [(182.62±53.96) U, (166.79±48.20) U, (159.13±43.92) U, P<0.001], while the duration of Gn used and clinical pregnancy rate had no significant differences (all P>0.05). Multifactorial stepwise aggression analysis showed that female age [0.93(0.90-0.96), P=0.007], AFC [1.07(1.03-1.09), P=0.001], AMH [1.29(1.20-1.39), P=0.001], basal follicle-stimulating hormone [0.79(0.73-0.86), P=0.001], luteinizing hormone value [1.11(1.06-1.23), P=0.010], initial dosage of Gn used [1.00(1.00-1.01), P=0.003], total dosage of Gn usd [1.00(0.99-1.00), P=0.001] and the presence or absence of diagnosis of endometriosis [0.63(0.47-0.86), P=0.001] and polycystic ovary syndrome [0.30(0.22-0.91), P=0.030] were independent factors for the occurrence of different ovarian responses during ovarian hyperstimulation. The prediction model of ovarian reactivity was constructed based on the above factors, and the accuracy of predicting the optimal ovarian response state was 95%. The above model was verified with 306 patients' data from August 1, 2019 to October 30, 2019 in this center, and the predicted ovarian response (number of oocytes obtained) of a total of 279 patients was consistent with the actual situation, with a coincidence degree of 91.2%. The consistency index of the model was 0.71. Conclusion We screened out the relevant factors affecting ovarian response in patients undergoing assisted reproductive technology with follicular phase long-acting long protocol, and established a Nomogram prediction model of ovarian response, which could effectively, intuitively and visually predict ovarian reactivity in hyperstimulation. © 2022 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.     

Ovarian stimulation: is there a long-term risk for ovarian, breast and endometrial cancer?

Adverse effects have been related to infertility treatments. Infertility in general, and female infertility in particular, is a well established risk factor for cancer development, especially ovarian, breast and endometrial cancer. This article addresses the possible association between infertility and cancer development, with an emphasis on the influence of infertility treatments, through a meticulous search of the literature published thus far. While results regarding the possible association of infertility, ovulation induction medications and invasive ovarian cancer show no increased risk and are reassuring, results for increased risk for breast cancer and endometrial cancer following exposure to ovarian stimulation medications are inconclusive. Larger population studies with longer periods of follow-up and better adjustment for confounding factors are needed.