In Vitro Fertilization’ Influence on Women’s Health

The IVF or In Vitro fertilization is a process that allows women to get pregnant even if they experience barriers or limits in this process or are infertile. IVF is a procedure where the woman’s egg is combined with sperm outside of her body (sperm can be obtained from the husband of the patient, another family member, or a donor, depending on the situation). The fertilized egg is then removed to the woman’s uterus (or the uterus of a surrogate mother), and the expected pregnancy development is controlled by the professional.

IVF became a popular treatment for infertility, allowing many women to have children even if their health status did not allow them to become mothers. At the same time, the IVF delivery rates are quite small, only 33% (Zheng, Huang, Zhang, & Wang, 2012). In this paper, I aim to examine the possible influences of IVF on women and their children, as well as establish what techniques, behaviors, or interventions can make this type of infertility treatment more efficient.

1. 2. 3. 4. 5.
Author, Title, & Year Authors:
Sandin, Nygren, Iliadou, Hultman, & Reichenberg

Title:
Autism and mental retardation among offspring born after In Vitro fertilization

Year:
2013

Authors:
Pasch, Gregorich, Katz, Millstein, Nachtigall, Bleil, & Adler.

Title:
Psychological distress and in vitro fertilization outcome.

Year:
2012

Authors:
Domar, Conboy, Denardo-Roney, & Rooney.

Title:
Lifestyle behaviors in women
undergoing in vitro fertilization:
A prospective study.
Year:
2012

Authors:
Zheng, Huang, Zhang, & Wang.

Title:
Effects of acupuncture on pregnancy rates in women undergoing in vitro fertilization: A systematic review and meta-analysis.

Year:
2012

Brinton, Trabert, Shalev, Lunenfeld, Sella, & Chodick.

Title:
In vitro fertilization and risk of breast and gynecologic cancers: a retrospective cohort study within the Israeli Maccabi Healthcare Services.

Year:
2013

Theoretical or Conceptual Framework The Poisson regression. The Poisson regression is used to estimate rate data (a count of events). A binary logistic model and linear regression models were used to assess the covariates. The study was based on the lifestyle framework during pregnancy that focuses on different lifestyle behaviors such as exercising, drinking alcohol, drinking beverages with caffeine, etc. The meta-analysis framework was used to review, assess, and collect information from various randomized control trials. Cox proportional hazards regression
Design / Method A population-based, prospective cohort study.
All live births in Sweden from 1982 to 2007 were used; children were followed up until 2009.
A prospective cohort study that lasted 18 months. Questionnaire packets and interviews with participants, follow-up assessments, and medical records were used to gather and evaluate data. A prospective survey/assessment of lifestyle habits during an ART cycle. Participants were from Boston IVF (BIVF), a large academic, private practice. The study continued from 2009 to 2010 (June-March). A systematic review, meta-analysis. Digital databases (Pubmed, Embase, the Cochrane Library, the Clinical Trials Register, and Chinese databases were used to collect data. The authors used the following keywords: acupuncture, acupoint, and IVF, in vitro fertilization, etc. A retrospective cohort study conducted with the data from one of the biggest healthcare services in Israel. The medical history records were obtained from the MHS central data registry.
Sample and Sample Size 2.5 million infants were born during the period. 30 959 infants were conceived using IVF. 202 participants, who visited the clinic for the first time, never used IVF, were not sterilized or never had a hysterectomy, had no recurrent miscarriages, were English speaking, and had a male partner. 118 women initially, 106 women who were treated at BIVF, 18-44 y.o., used their own eggs when undergoing IVF, had Internet access. 24 trials (5,807 participants and 5,547 finished ETs) were used. RCTs were used as primary sources of data. 87,403 eligible study subjects were used, 1994
diagnosed with cancer, and 1,509 cancer incidents
used. Exclusive categories were male infertility, mechanical causes, endometriosis, pituitary-hypothalamic problems,
and polycystic ovary syndrome.
Independent and Dependent Variables Independent variables:
The IVF procedure, parental age, the history of psychiatric diseases, multiple births, preterm births.

Dependent variables:
The number of offspring with Autism or mental retardation; the rate of the risk of autistic disorder/mental retardation, the relation of IVF treatment to mental disorders.

Independent variables:
The type of IVF procedure, IVF cycle outcome.

Dependent variables:
Post-IVF anxiety and depression

Independent variables:
The time prior to the IVF cycle, the type of IVF.

Dependent variables:
Lifestyle habits such as exercising, drinking alcohol, smoking, taking herbs, using acupuncture.

Independent variables:
Acupuncture techniques (manual, electrical, laser).

Dependent variables:
Clinical pregnancy rate, live birth rate, the therapeutic effect.

Independent variables:
The IVF procedure,
the IVF type, the number of IVF cycles.

Dependent variables:
The risk of developing breast and gynecologic cancers.

Measurement: Instruments and Tools Swedish national registers, follow-ups, information from the National Board of Health and Welfare, SAS GLIMMIX version 9.3 (software). The Center for Epidemiologic Study of Depression Scale (CES-D; 10) was used to measure depression, while the State Anxiety subscale of the State-Trait Anxiety Inventory (STAI; 12) aimed to measure anxiety. Questionnaires, interviews, and follow-up assessments were used to gather information. Lifestyle and Health Habits Questionnaire created specifically for the study, SPSS data analysis package (software), to analyze the collected data. A forest plot analysis was used to assess the heterogeneity of the therapeutic effect, and a funnel plot analysis was engaged in evaluating publication bias, Review Manager 5.1 (software). Cox proportional hazards regression, SAS statistical software, version 9.1.3.
Data Analysis After the researchers estimated RRs and 2-sided 95% Wald confidence intervals, the regression models were fitted. Follow-up time was split into one-year intervals. Each child was examined up to their death, 28 years, emigration, and the start of the disease. Parental age and psychiatric history were included, too as confounding covariates. A binary logistic model included covariates such as age, ethnicity, parity, income, etc. and was used to assess pre-treatment depression and anxiety. Linear regression models included such covariates as education, income, parity, duration of infertility, etc. and were used to evaluate post-IVF depression and anxiety after failed IVF. The authors calculated simple tabulations and frequencies, and reported behaviors were compared to other temporal variables (past months/ daily record, etc.); two-sided t-tests were engaged in analyzing if the reported behavior was different to the one during the last five years. Pregnancy outcomes were pooled from the analyses, and a fixed-effects model or a random-effects model for meta-analyses was used, depending on the heterogeneity of the trials’ characteristics. Intention-to-treat analysis (ITT) and a treated-per-protocol analysis (TPP) were used to underestimate or overestimate the effect of acupuncture. Cox proportional hazards regression
was used to estimate hazard ratios (HR) and
95% confidence intervals (CI) of possible cancer development for women who underwent IVF. Two-sided P-values and an alpha less than 0.05 were the indications of statistical significance.
Findings 1.5% (103 of 6959) and 1.1% (80 of 15 830) of children conceived with IVF were either autistic or developed mental retardation. If ICSI and frozen embryos were used, the risk of mental retardation increased (RR 2.36). Pre-treatment depression and anxiety were not related to succeeded/failed IVF. If participants experienced failed IVF, the rate of depression and anxiety after the procedure was higher. Before IVF, participants exercised (92%), took herbs (14%), smoked (3%), drank alcohol (73%), and underwent acupuncture (30%). During the procedure, the participants continued to exercise (100%), 12% took herbs, 2% smoked, 77% drank caffeine, 49%/47% drank alcohol and underwent acupuncture respectively. The pooled CPR (acupuncture) was higher compared to the control group. The authors suggest increasing the stimulation at acupoints. No
significant
relations between IVF and the development of breast or gynecological cancer. However, a higher risk was
identified
for women who underwent 4+ IVF cycles.
Strengths / Limitations Strengths:
Large sample size and follow-ups guarantee results that are more reliable. The study points out that the relation between autism and IVF is not as high as some believe it to be. The study has the potential to promote IVF by reducing some of the anxieties linked to it.

Weaknesses:the study was conducted in Sweden only. It is impossible to evaluate whether the findings are related to specifics of IVF in Sweden and whether they apply to other countries. Socioeconomic status and education of parents were not assessed.

Strengths:
The influence of pre-treatment depression and anxiety remained disputable, and previous studies had particular methodological problems (small sample sizes, wrong approach to a positive outcome, etc.). The study controlled other predictors of IVF outcomes (age, parity, duration of infertility).

Weaknesses:
Relatively small sample size, not a randomized trial, no manipulation of variables.

Strengths:
The lifestyle habits of women undergoing the IVF were rarely studied previously. The study is a prospective survey (unlike other retrospective studies focused on similar topics). The results of the research can be used by professionals to provide information about lifestyle interventions.

Weaknesses:
Low response rate, small sample size, missing data in some of the reports.

Strengths:
RTCs chosen as the primary sources, multiple databases were used to collect data, meta-analysis as a framework to summarize the evidence.

Weaknesses:
Differences in acupuncture techniques, too short acupuncture sessions, lack of a correct method to establish placebo control group when studying acupuncture.

Strengths:
Large sample size, representatives of all social classes and subgroups were
included,
control of other cancer predictors.

Weaknesses:
The short follow-up, incomplete information,
no access to recognized risk factors in a patient.

The studies have shown that IVF is a procedure popular among women who experience difficulties trying to conceive or have infertility. The exposure to IVF should not be associated with the development of autism and mental retardation in offspring. Furthermore, the development of cancer should not be perceived as a possible consequence of IVF as well. Although such assumptions and beliefs still exist, Brinton et al. (2013) proved that there were no significant relations between the development of cancer and IVF.

Nevertheless, the authors also pointed out that patients who experienced more than four cycles of IVF are at higher risk compared to those who had had fewer IVF cycles. Many women pay attention to their lifestyle and behaviors during IVF cycle, but it does not mean that they prefer to focus on healthy lifestyle interventions only. This raises additional concerns about patients’ awareness of possible negative influences that such lifestyle habits may have.

For example, half of the participants decided to continue drinking alcohol, and 2% of the women did not quit smoking. Additional consultations are necessary to ensure that patients understand the importance of lifestyle changes. Acupuncture is frequently used by women who undergo IVF as a supplementary intervention; one of the reviewed studies showed that it could be effective if the intensity of the intervention were increased (Zheng et al., 2012).

According to the authors, acupuncture has the potential to improve clinical pregnancy rate and live birth rate (Zheng et al., 2012). Although it is seen as a complementary or alternative medical treatment, many patients prefer undergoing it during their pregnancies. However, the authors also pointed out that it was difficult to obtain reliable data since there was no established way to create a control group (treated with placebo) during acupuncture studies and RCTs. Thus, patients have the need to refer to CAMs in order to feel psychological or physiological support during their pregnancy. The belief about the negative influence of pre-treatment depression on IVF still exists (Wu et al., 2014).

Some of the patients have persistent beliefs and opinions that pre-treatment depression or anxiety are capable of negatively influencing pregnancy and its outcomes. However, there is no evidence that pre-treatment anxiety and depression can affect the outcomes of IVF. Additional studies are necessary to evaluate the relations between depression and IVF outcomes. The authors of the study also notice that one should pay attention to the number of IVF cycles that the patient had undergone before (Pasch et al., 2012). As it can be seen, the IVF procedure should be perceived as a safe option for treating infertility or other difficulties with conception.

Most of the risks related to it were proven to be unsubstantiated, such as the relation between IVF and autism or cancer. Nevertheless, the positive influence of acupuncture on pregnancy outcomes should also be reviewed since there is no appropriate way to establish a control group treated with placebo when studying acupuncture.

References

Brinton, L. A., Trabert, B., Shalev, V., Lunenfeld, E., Sella, T., & Chodick, G. (2013). In vitro fertilization and risk of breast and gynecologic cancers: A retrospective cohort study within the Israeli Maccabi Healthcare Services. Fertility and Sterility, 99(5), 1189-1196.

Domar, A. D., Conboy, L., Denardo-Roney, J., & Rooney, K. L. (2012). Lifestyle behaviors in women undergoing in vitro fertilization: A prospective study. Fertility and Sterility, 97(3), 697-701.

Pasch, L. A., Gregorich, S. E., Katz, P. K., Millstein, S. G., Nachtigall, R. D., Bleil, M. E., & Adler, N. E. (2012). Psychological distress and in vitro fertilization outcome. Fertility and Sterility, 98(2), 459-464.

Sandin, S., Nygren, K. G., Iliadou, A., Hultman, C. M., & Reichenberg, A. (2013). Autism and mental retardation among offspring born after in vitro fertilization. JAMA, 310(1), 75-84.

Wu, G., Yin, T., Yang, J., Xu, W., Zou, Y., Wang, Y., & Wen, J. (2014). Depression and coping strategies of Chinese women undergoing in-vitro fertilization. European Journal of Obstetrics & Gynecology and Reproductive Biology, 183(1), 155-158.

Zheng, C. H., Huang, G. Y., Zhang, M. M., & Wang, W. (2012). Effects of acupuncture on pregnancy rates in women undergoing in vitro fertilization: A systematic review and meta-analysis. Fertility and Sterility, 97(3), 599-611.

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