Medically assisted reproduction and birth outcomes

A within-family analysis using Finnish population registers

Large registry study finds lighter birth weight and higher prematurity rates observed after IVF largely attributable to factors other than treatment.

Summary

Background
Children born after medically assisted reproduction are at higher risk of adverse birth outcomes than are children conceived naturally. We aimed to establish the extent to which this excess risk should be attributed to harmful effects of treatment or to pre-existing parental characteristics that confound the association.

Methods
We used data from Finnish administrative registers covering a 20% random sample of households with at least one child aged 0–14 years at the end of 2000 (n=65 723). We analysed birthweight, gestational age, risk of low birthweight, and risk of preterm birth among children conceived both by medically assisted reproduction and naturally. First, we estimated differences in birth outcomes by mode of conception in the general population, using standard multivariate methods that controlled for observed factors (eg, multiple birth, birth order, and parental sociodemographic characteristics). Second, we used a sibling-comparison approach that has not been used before in medically assisted reproduction research. We compared children conceived by medically assisted reproduction with siblings conceived naturally and, thus, controlled for all observed and unobserved factors shared by siblings.

Findings
Between 1995 and 2000, 2776 (4%) children in our sample were conceived by medically assisted reproduction; 1245 children were included in the sibling comparison. Children conceived by medically assisted reproduction had worse outcomes than did those conceived naturally, for all outcomes, even after adjustments for observed child and parental characteristics—eg, difference in birthweight of −60 g (95% CI −86 to −34) and 2·15 percentage point (95% CI 1·07 to 3·24) increased risk of preterm delivery. In the sibling comparison, the gap in birth outcomes was attenuated, such that the relation between medically assisted reproduction and adverse birth outcomes was statistically and substantively weak for all outcomes—eg, difference in birthweight of −31 g (95% CI −85 to 22) and 1·56 percentage point (95% CI −1·26 to 4·38) increased risk of preterm delivery.

Interpretation
Children conceived by medically assisted reproduction face an elevated risk of adverse birth outcomes. However, our results indicate that this increased risk is largely attributable to factors other than the medically assisted reproduction treatment itself.

Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy

The Practice Committee of the American Society for Reproductive Medicine Opinion, 2018

“Patients preparing to undergo gonadotoxic medical therapy or radiation therapy or gonadectomy should be provided with prompt counseling regarding available options for fertility preservation. Fertility preservation can best be provided by comprehensive programs designed and equipped to confront the unique challenges facing these patients.

Over 100,000 individuals less than 45 years of age are diagnosed with cancer annually in the United States. Over the past 4 decades, advancements in cancer therapies, particularly chemotherapeutics, have led to dramatic improvements in survival. Given the reproductive risks of cancer therapies and improved long-term survival, there has been growing interest in expanding the reproductive options for cancer patients. Indeed, both cancer survivors and the medical community have acknowledged the importance of patient counseling” …

continue reading on the American Society for Reproductive Medicine practice guidelines.

The impact of assisted reproductive technology on the offspring

Association of birth defects with the mode of assisted reproductive technology in a Chinese data-linkage cohort

2018 Study Abstract

Objective
To evaluate the impact of assisted reproductive technology (ART) on the offspring of Chinese population.

Design
Retrospective, data-linkage cohort.

Setting
Not applicable.

Patient(s)
Live births resulting from ART or natural conception.

Intervention(s)
None.

Main Outcome Measure(s)
Birth defects coded according to ICD-10.

Result(s)
Births after ART were more likely to be female and multiple births, especially after intracytoplasmic sperm injection (ICSI). ART was associated with a significantly increased risk of birth defects, especially, among singleton births, a significantly increased risk in fresh-embryo cycles after in vitro fertilization (IVF) and frozen-embryo cycles after ICSI. Associations between ART and multiple defects, between ART and gastrointestinal malformation, genital organs malformation, and musculoskeletal malformation among singleton births, and between ART and cardiac septa malformation among multiple births were observed.

Conclusion(s)
This study suggests that ART increases the risk of birth defects. Subgroup analyses indicate higher risk for both fresh and frozen embryos, although nonsignificantly for frozen embryos after IVF and for fresh embryos were presented with low power. Larger sample size research is needed to clarify effects from fresh- or frozen-embryo cycles after IVF and ICSI.

Maternal antidepressant use associated with increased risk of miscarriage

Major depression, antidepressant use, and male and female fertility : Cohort study

2018 Study Abstract

Objective
To determine if maternal major depression (MD), antidepressant use, or paternal MD are associated with pregnancy outcomes after non-IVF fertility treatments.

Design
Cohort study, DOI: https://doi.org/10.1016/j.fertnstert.2018.01.029, May 2018.

Setting
Clinics.

Patient(s)
Participants in two randomized trials: PPCOS II (clomiphene citrate versus letrozole for polycystic ovary syndrome), and AMIGOS (gonadotropins versus clomiphene citrate versus letrozole for unexplained infertility).

Intervention(s)
Female and male partners completed the Patient Health Questionnaire (PHQ-9). Female medication use was collected. PHQ-9 score ≥10 was used to define currently active MD.

Main Outcome Measure(s)
Primary outcome: live birth. Secondary outcomes: pregnancy, first-trimester miscarriage. Poisson regression models were used to determine relative risks after adjusting for age, race, income, months trying to conceive, smoking, and study (PPCOS II versus AMIGOS).

Result(s)
Data for 1,650 women and 1,608 men were included. Among women not using an antidepressant, the presence of currently active MD was not associated with poorer fertility outcomes (live birth, miscarriage), but rather was associated with a slightly increased likelihood of pregnancy. Maternal antidepressant use (n = 90) was associated with increased risk of miscarriage, and male partners with currently active MD were less likely to achieve conception.

Conclusion(s)
Currently active MD in the female partner does not negatively affect non-IVF treatment outcomes; however, currently active MD in the male partner may lower the likelihood of pregnancy. Maternal antidepressant use is associated with first-trimester pregnancy loss, which may depend upon the type of antidepressant.

The future of human uterine transplantation

Can minimally invasive techniques provide a uterus suitable for transplant?

2017 Abstract

Interest in uterine transplantation for the treatment of uterine factor infertility (UFI) has grown exponentially over the past several years. Following the first birth from this procedure in September 2014, multiple centers worldwide have announced plans to perform clinical trials of uterine transplant. A prominent consideration in creating a protocol is whether to select a living or a nonliving donor model and whether a minimally invasive technique can be successfully used to minimize living donor risk.

Although this study and others will increase optimism for the possibility of a minimally invasive uterus retrieval, no current protocols in humans or animals have yet reported a successful pregnancy using a minimally invasive approach. Although resumption of menstrual function occurred in this case report within two months of transplant, it is unknown whether a uterus drained by the utero-ovarian vessels will be able to support and sustain implantation and ongoing pregnancy in humans.

  • The future of human uterine transplantation: can minimally invasive techniques provide a uterus suitable for transplant?, American Society for Reproductive Medicine, Volume 108, Issue 2, Pages 243–244, August 2017.
  • Image of Cleveland Clinic surgeons at work performing the first uterus transplant in the US. credit vox.

Lesbian, gay, bisexual, transgender content on reproductive endocrinology and infertility clinic websites

Fertility and Sterility, Sexuality, Volume 108, Issue 1, July 2017

2017 Study Abstract

Objective
To assess geographical distribution and practice characteristics of fertility clinics inclusive of lesbian, gay, bisexual, and transgender (LGBT) patients.

Design
Cross-sectional analysis.

Main Outcome Measure(s)

Lesbian, gay, bisexual, transgender content on reproductive endocrinology and infertility clinic websites, Fertility and Sterility, Sexuality, Volume 108, Issue 1, dx.doi.org/10.1016/j.fertnstert.2017.05.011, July 2017.

Rainbow flag credit CJF20.

Prevalence and geographical distribution of fertility clinic websites with LGBT-specific content, indicated by keywords and home page cues specific to the LGBT patient population. Assessment of relationship between LGBT-specific content and clinic characteristics, including U.S. region, clinic size, private versus academic setting, and state-mandated fertility insurance coverage.

Result(s)
Of 379 websites analyzed, 201 (53%) contained LGBT content. Clinics with the highest proportion of LGBT website content were in the Northeast (59/82, 72%) and West (63/96, 66%), while the lowest proportion was in the Midwest (29/74, 39%) and South (50/127, 39%). Most frequently used terms included lesbian (72%), LGBT/LGBTQ (69%), and gay (68%), while less used terms included trans/transgender (32%) and bisexual (15%). Larger clinic size was associated with LGBT-specific website content (odds ratio, 4.42; 95% confidence interval, 2.07–9.67). Practice type and state-mandated fertility insurance coverage were not associated with a clinic website having LGBT content.

Conclusion(s)
Over half of Society for Assisted Reproductive Technology member fertility clinics included LGBT content on their websites, yet those in the Midwest and South were significantly less likely to do so. Predictive factors for having LGBT website content included location in northeastern and western regions and increasing clinic size. Further studies are needed to evaluate whether inclusion of LGBT content on clinic websites impacts use of reproductive services by the LGBT patient population.

Woman delivers a baby 15 years after having frozen an ovary tissue before puberty

Baby born from ovary frozen in childhood

” When she was 9 years old, Moaza Al Matrooshi found out she would need chemotherapy in order to receive a bone-marrow transplant and treat a potentially fatal blood disorder.

Her family worried the chemotherapy would cause her to become infertile, so they made a decision that was considerably rare at the time: Professor Helen Picton, Head of the Division of Reproduction and Early Development at the University of Leeds removed her right ovary and froze the tissue.

Last Tuesday, about 15 years later, Al Matrooshi, of Dubai, gave birth to a healthy baby at London’s Portland Hospital for Women and Children. The 24-year-old woman is believed to be the first in the world to deliver a baby after having frozen an ovary tissue before puberty.” …

… continue reading Woman believed to be the first to have a baby using ovary frozen before puberty, The Independent, 19 December 2016.

Cross-border reproductive care: an Ethics Committee opinion

Fertility and Sterility, Ethics Committee of the American Society for Reproductive Medicine, 2016

Abstract

Cross-border reproductive care (CBRC) is a growing worldwide phenomenon, raising questions about why assisted reproductive technology (ART) patients travel abroad, what harms and benefits may result, and what duties health-care providers may have in advising and treating patients who travel for reproductive services.

The factors that motivate patients to travel abroad for fertility care are varied, complex and often interrelated. The reasons for CBRC fall into four basic categories:

  • access,
  • cost,
  • regulation,
  • and privacy.

The delivery of CBRC does not invoke a duty to inform or warn patients about the potential legal or practical hazards that may accompany such care.

Cross-border care offers benefits and poses harms to ART stakeholders, including patients, offspring, providers, gamete donors, gestational carriers, and local populations in destination countries.

This document replaces the previous document of the same name, last published in 2013. Take off image by lattefarsan.

In vitro fertilization success rate for older women is consistently low

The Misleading Promise of I.V.F. for Women Over 40

” Many young women were understandably seduced by the once widely publicized message that if they chose to delay pregnancy and were then unable to conceive, they could still have babies through in vitro fertilization, also known as I.V.F.

Miriam Zoll was one of them. Married at age 35, she thought she had plenty of time to start a family. After all, she said, “My mother had me at 40, and since 1978, the fertility industry has been celebrating its ability to help women have children at older ages.”

When at 39 she and her husband decided to start a family, they discovered that nature refused to cooperate. Four emotionally and physically exhausting I.V.F. cycles (and two attempted donor egg cycles) later, they remained childless. ” …

… continue reading The Misleading Promise of I.V.F. for Women Over 40NY Times, OCT. 17, 2016.

How women are being misled about the success rates of IVF and fertility treatments

Some people are getting IVF who shouldn’t be getting it

The Baby Business – Four Corners, May 31, 2016.

An Australian documentary has claimed that women over 40 are being misled about their chances of conceiving via IVF treatment when using their own eggs.

An investigation by the current affairs documentary Four Corners, on ABC, explained that chances of having a live birth per cycle following IVF treatment using their own fresh eggs were:

  • almost 6% for women aged 41-42 years old,
  • reduced to just under 3% for women aged 43–44 years old,
  • limited to a mere 1% for women over the age of 45.

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