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Fertility/Reproductive Medicine

Cohort Study: Levonorgestrel IUD Use Linked to Increased Breast Cancer Risk in Premenopausal Women

20 Oct, 2024 | 18:13h | UTC

Background: Levonorgestrel-releasing intrauterine systems (LNG-IUSs) are increasingly used, especially among Danish premenopausal women over 30 years old, as a preferred method of hormonal contraception. Previous studies have suggested an increased risk of breast cancer with LNG-IUS use but did not adequately address the duration of continuous use or account for other hormonal contraceptive exposures.

Objective: To assess the risk of breast cancer associated with continuous use of LNG-IUSs, accounting for other hormonal exposures.

Methods: In this nationwide Danish cohort study, 78,595 first-time LNG-IUS users aged 15–49 years from 2000 to 2019 were identified and matched 1:1 by birth year to nonusers of hormonal contraceptives. Exclusion criteria included prior hormonal contraceptive use within 5 years, previous cancer, postmenopausal hormone therapy, and pregnancy at baseline. Participants were followed from initiation until breast cancer diagnosis, other cancer, pregnancy, hormone therapy initiation, emigration, death, or December 31, 2022. Cox proportional hazards models adjusted for confounders estimated hazard ratios (HRs) for breast cancer associated with continuous LNG-IUS use.

Results: During a mean follow-up of 6.8 years, 1,617 breast cancer cases occurred: 720 among LNG-IUS users and 897 among nonusers. The mean age was 38 years. Continuous LNG-IUS use was associated with a higher breast cancer risk compared to nonuse (HR, 1.4; 95% CI, 1.2–1.5). HRs by duration were 1.3 (95% CI, 1.1–1.5) for 0–5 years, 1.4 (95% CI, 1.1–1.7) for >5–10 years, and 1.8 (95% CI, 1.2–2.6) for >10–15 years. Excess breast cancer cases per 10,000 users were 14 (95% CI, 6–23), 29 (95% CI, 9–50), and 71 (95% CI, 15–127), respectively. The trend test for duration was not statistically significant (P = .15).

Conclusions: Continuous use of LNG-IUSs was associated with an increased risk of breast cancer among women aged 15–49 years compared to nonuse of hormonal contraceptives. The absolute increase in risk was low.

Implications for Practice: Healthcare providers should inform women about the potential increased breast cancer risk associated with LNG-IUS use, especially considering its widespread and long-term use among premenopausal women. While the absolute risk increase is small, this information is essential for making informed contraceptive choices.

Study Strengths and Limitations: Strengths include the large, nationwide cohort and adjustment for multiple confounders. Limitations include potential underestimation of risk due to unrecorded LNG-IUS removals before the recommended duration, lack of a statistically significant trend with duration suggesting possible low statistical precision or non-causal association, and the possibility of unmeasured confounding.

Future Research: Further studies are needed to confirm these findings, clarify the causal relationship, and understand the mechanisms underlying the potential increased breast cancer risk with LNG-IUS use.

Reference: Mørch LS, Meaidi A, Corn G, et al. Breast Cancer in Users of Levonorgestrel-Releasing Intrauterine Systems. JAMA. Published online October 16, 2024. DOI: http://doi.org/10.1001/jama.2024.18575

 


Cohort Study: Elevated autism spectrum disorder risk in children exposed to valproate during pregnancy

21 Mar, 2024 | 13:16h | UTC

Study Design and Population: This cohort study utilized two health care utilization databases in the United States, covering the period from 2000 to 2020, to investigate the association between prenatal exposure to antiseizure medications and the risk of autism spectrum disorder (ASD) in children. The study compared children exposed to topiramate, valproate, or lamotrigine during the second half of pregnancy to those unexposed to any antiseizure medication, specifically focusing on a population-based cohort of pregnant women and their offspring.

Main Findings: The cumulative incidence of ASD at 8 years of age was found to be higher in children exposed to these medications compared to the general population. Notably, the incidence was 6.2% for children exposed to topiramate, 10.5% for valproate, and 4.1% for lamotrigine among children born to mothers with epilepsy. However, after adjusting for potential confounders, the increased risk of ASD remained significant only for valproate exposure, with a hazard ratio of 2.67, indicating a substantial risk compared to unexposed children. Topiramate and lamotrigine showed no significant increase in risk after adjustment.

Implications for Practice: The findings underscore the importance of carefully considering the risks and benefits of using antiseizure medications during pregnancy. Specifically, valproate should be used with caution, if at all, given its significant association with an increased risk of ASD in offspring. This study supports the need for targeted counseling and monitoring of pregnant women with epilepsy and highlights the necessity for further research to fully understand the neurodevelopmental impact of prenatal exposure to antiseizure medications.

Reference: Sonia Hernández-Díaz et al. (2024). Cohort Study: Assessing Autism Spectrum Disorder Risk in Children Exposed to Antiseizure Medications During Pregnancy. N Engl J Med, 390(13), 1069-1079. DOI: 10.1056/NEJMoa2309359. Access the study here: [Link]


Review | Radiomics-based fertility-sparing treatment in endometrial carcinoma

24 Jul, 2023 | 13:00h | UTC

Radiomics-based fertility-sparing treatment in endometrial carcinoma: a review – Insights into Imaging

 


RCT | Time-lapse-based embryo selection does not improve pregnancy rates in IVF treatments

23 Jun, 2023 | 13:37h | UTC

Clinical outcomes of uninterrupted embryo culture with or without time-lapse-based embryo selection versus interrupted standard culture (SelecTIMO): a three-armed, multicentre, double-blind, randomised controlled trial – The Lancet (link to abstract – $ for full-text)

News Release: New IVF Method: more expensive, not more effective – Amsterdam UMC

 

Commentary on Twitter (thread – click for more)

 


RCT | Prednisone fails to enhance live birth outcomes in women with recurrent implantation failure

5 May, 2023 | 15:31h | UTC

Prednisone vs Placebo and Live Birth in Patients With Recurrent Implantation Failure Undergoing In Vitro Fertilization: A Randomized Clinical Trial – JAMA (free for a limited period)

See also: Visual Abstract

 


WHO Report | 1 in 6 people globally affected by infertility

5 Apr, 2023 | 13:47h | UTC

News Release: 1 in 6 people globally affected by infertility – World Health Organization

Report: Infertility Prevalence Estimates, 1990–2021 – World Health Organization

Key facts: Infertility – World Health Organization

Commentaries:

Infertility affects a ‘staggering’ 1 in 6 people worldwide, WHO says – CNN

One in six people worldwide affected by infertility, WHO reports – The Guardian

 

Commentary on Twitter (thread – click for more)

 


Study shows there is little evidence of heightened pregnancy risks for IVF-conceived parents

24 Mar, 2023 | 12:53h | UTC

Reproductive outcomes in women and men conceived by assisted reproductive technologies in Norway: prospective registry based study – BMJ Medicine

News Release: Little evidence that IVF conception heightens future pregnancy risks – BMJ Newsroom

 


Cohort Study | Infertility in women linked to increased risk of cardiovascular disease

23 Mar, 2023 | 12:39h | UTC

Infertility and Risk of Cardiovascular Disease: A Prospective Cohort Study – Journal of the American Heart Association

 

Commentary on Twitter

 


Cohort Study | IVF-conceived children have similar school-age educational outcomes as spontaneously conceived children

2 Mar, 2023 | 12:53h | UTC

School-age outcomes among IVF-conceived children: A population-wide cohort study – PLOS Medicine

News Release: No link between IVF-assisted conception and school-age childhood development outcomes, study says – University of Melborn

Commentary: IVF Not Tied to Worse Developmental, Educational Outcomes – HealthDay

 


Registry of the international society of uterus transplantation: first report

24 Feb, 2023 | 13:29h | UTC

Registry of the International Society of Uterus Transplantation: First Report – Transplantation

 


Development of a model to estimate the optimal number of oocytes to attempt to fertilize in IVF

14 Feb, 2023 | 10:36h | UTC

Development of a Model to Estimate the Optimal Number of Oocytes to Attempt to Fertilize During Assisted Reproductive Technology Treatment – JAMA Network Open

 

Commentary on Twitter

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799935

 


Stillbirth after adolescent and young adult cancer: a population-based study

14 Feb, 2023 | 10:33h | UTC

Stillbirth After Adolescent and Young Adult Cancer: A Population-Based Study – JNCI: Journal of the National Cancer Institute

News Release: Cancer in adolescent and young adult women before pregnancy does not increase risk for stillborn births, according to UTHealth Houston research

Commentary: Previous Cancer Treatment Not Tied to Higher Stillbirth Rate – HealthDay

 


RCT | Routine use of endometrial receptivity testing to guide the timing of frozen embryo transfer did not improve the rates of live birth

20 Jan, 2023 | 14:45h | UTC

Effect of Timing by Endometrial Receptivity Testing vs Standard Timing of Frozen Embryo Transfer on Live Birth in Patients Undergoing In Vitro Fertilization: A Randomized Clinical Trial – JAMA (link to abstract – $ for full-text)

 

Commentary on Twitter

 


Cohort Study | Neurodevelopmental disorders in offspring conceived via IVF vs. intracytoplasmic sperm injection

19 Jan, 2023 | 14:12h | UTC

Neurodevelopmental Disorders in Offspring Conceived via In Vitro Fertilization vs Intracytoplasmic Sperm Injection – JAMA Network Open

 


Review | Pathophysiology, diagnosis, and management of endometriosis.

16 Dec, 2022 | 13:23h | UTC

Pathophysiology, diagnosis, and management of endometriosis – The BMJ

 


Cohort Study | Obstetric and perinatal outcomes of singleton births following single- vs. double-embryo transfer.

6 Dec, 2022 | 13:45h | UTC

Obstetric and Perinatal Outcomes of Singleton Births Following Single- vs Double-Embryo Transfer in Sweden – JAMA Pediatrics

 

Commentary on Twitter

 


Guideline Synopsis | Diagnosis and treatment of infertility in men.

23 Nov, 2022 | 14:08h | UTC

Diagnosis and Treatment of Infertility in Men – JAMA (free for a limited period)

Original Guideline: AUA/ASRM Guideline: Diagnosis and treatment of infertility in men

 


SR | Follicular flushing during oocyte retrieval in assisted reproductive techniques.

23 Nov, 2022 | 13:46h | UTC

Follicular flushing during oocyte retrieval in assisted reproductive techniques – Cochrane Library

 

Commentary on Twitter

 


Perspective | The case for mild stimulation for in vitro fertilization.

14 Oct, 2022 | 14:07h | UTC

The case for mild stimulation for IVF: recommendations from The International Society for Mild Approaches in Assisted Reproduction – Reproductive Biomedicine Online

 

Commentary on Twitter

 


Systematic Review | Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome.

30 Sep, 2022 | 12:29h | UTC

Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome – Cochrane Library

 

Commentary on Twitter

 


European Crohn’s and Colitis Guidelines on sexuality, fertility, pregnancy, and lactation.

29 Sep, 2022 | 13:30h | UTC

European Crohn’s and Colitis Guidelines on Sexuality, Fertility, Pregnancy, and Lactation – Journal of Crohn’s and Colitis

 


Cohort Study | Children conceived via assisted reproductive technologies are at increased risk of childhood cancers.

7 Sep, 2022 | 12:32h | UTC

Assisted Reproductive Technology and Risk of Childhood Cancers – JAMA Network Open

Invited Commentary: Fertility Treatment and Childhood Cancer Risk – JAMA Network Open

 

Commentary on Twitter

 


Cohort Study | Fertility preservation procedures appear to be safe at the time of breast cancer diagnosis.

7 Sep, 2022 | 12:31h | UTC

Relapse Rates and Disease-Specific Mortality Following Procedures for Fertility Preservation at Time of Breast Cancer Diagnosis – JAMA Oncology

News Release: Fertility preservation measures do not appear to increase the risk of breast cancer recurrence – Karolinska Institutet

Commentary: Fertility Preservation Measures Do Not Appear to Increase the Risk of Breast Cancer Recurrence – The ASCO Post

 


Systematic Review | Luteal phase support for women trying to conceive by intrauterine insemination or sexual intercourse.

2 Sep, 2022 | 13:08h | UTC

Luteal phase support for women trying to conceive by intrauterine insemination or sexual intercourse – Cochrane Library

 

Commentary on Twitter

 


Cohort Study | Association of assisted reproductive technology with offspring growth and adiposity from infancy to early adulthood.

1 Aug, 2022 | 11:54h | UTC

Association of Assisted Reproductive Technology With Offspring Growth and Adiposity From Infancy to Early Adulthood – JAMA Network Open

News Release: Concerns about effects of fertility treatment on children’s development are unwarranted, large study suggest – University of Bristol

 

Commentary on Twitter

 


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