The issue of infertility in Reproductive Medicine: A Medical and (Inter)Cultural Perspective

2021-1-HU01-KA220-HED-000027613 - COHRICE

 

SYLLABUS

5. The issue of infertility in Reproductive Medicine: A Medical and (Inter)Cultural Perspective

(Advanced)



Slide 2.  - DEBATED TOPICS

In this curriculum, we examine the topic of infertility and Assisted Reproductive Technology (ART) from two perspectives: the medical and the patient's point of view.

The curriculum will lead you through the following steps, in order to obtain a multifaceted view of the question of infertility and infertility treatment:

First, we examine the issue of infertility from a medical perspective, and then we explore the same issue from the viewpoint of the infertile woman. After presenting both perspectives, we raise the question of what medical professionals can do to facilitate mutual understanding between the doctor and the patient, fostering a collaborative and effective relationship while providing infertility treatment.

Secondly, following a similar approach, we present the process of artificial fertilization (ART) from a medical perspective and provide insights into understanding what this means from the patient's point of view. All of this is aimed at ultimately demonstrating what the doctor can do to bridge the differences in perspectives.
We would like to point out that cultural, religious and social factors influence perception, communication and our compliance with medical interventions.

Slide 3. - STRUCTURE OF DISCUSSION - INTRODUCTION

From the medical perspective, the question of infertility and therapy involves diagnosis, exploration of causes, the utilization of scientifically tested methods to overcome infertility starting from less invasive to ultimately more invasive interventions. It is a problem-focused process where the ultimate goal being the live birth of a child in the family.

From the woman's perspective, the question of infertility and ART is not only a medical question, but also about personal, social and environmental factors.

This can easily lead to situations, where the doctor and the patient have difficulty in cooperating, misunderstandings may arise mostly due to the one sided communication, which leads to non-complience and treatment failure.  

Slide 4 - 5 INFERTILITY - MEDICAL PERSPECTIVE

The term "sterility" describes the inability to become pregnant after a year of trying, while the term "infertility" describes the inability to give birth to a living child. The two terms are often used interchangeably and no precise distinction is made between them. A distinction is made between primary sterility or infertility, when the woman has never been pregnant or concieved, and secondary sterility, when the woman concerned has already had previous pregnancies.

One in six couples worldwide will suffer from some form of infertility at least once during their reproductive lives, that's 48 million couples worldwide or 25 million Europeans. Discrimination, as well as distress and depression, might result from infertility. (World Health Organisation, 2023; Mascarenhas et al. 2012)

The increasing age of the female partner is one of the most common explanations For the increasing incidence of infertility today. The European Union is experiencing a population decline, with the highest birth rate in a sample of nine EU countries below the stabilization rate required for generational replacement, according to Eurostat. The current prevalence of infertility lasting at least 12 months is estimated at 8-12% of women aged 20-44 years worldwide.

Slide 6 - 7. - REASONS OF INFERTILITY

20-30% of male infertility cases are due to physiological causes, 20-35% of female infertility cases are due to physiological causes, and 25-40% of cases are due to a problem in both partners. In 10-20% of cases, no cause is found and we call these idiopathic infertility issues. Infertility is also associated with modifiable lifestyle factors such as smoking, body weight, drug consumption, excessive alcohol intake and stress.(Gelbaya et al. 2014; World Health Organisation, 2023; Gore et al. 2015; Segal et al. 2019) 4,5 ,1,6–8

Infertility in women's reproductive systems can result from:

  • Compromised structural or functional patency of the fallopian tubes, such as obstructed tubes, which are caused by untreated sexually transmitted infections or side effects of unsafe abortions, postpartum sepsis, or abdominal/pelvic surgery.
  • Uterine conditions that may be inflammatory (like endometritis), congenital (like a septate uterus), or benign (like fibroids, polyps)
  • Follicular diseases that affect the function of the ovaries, such as polycystic ovarian syndrome or premature ovarian insufficiency.
  • Pathologies of the hypothalamus - hypophysis axis, which in turn lead to  abnormalities in the female reproductive function. (World Health Organisation, 2023)

The proportional relevance of these factors in female infertility may vary in the different ethnicities, cultures, religions and social circles which can influence average childbearing age, sexual habits, prevalence of underlying diseases (such as the prevalence of  PCOS or POI, or fibroids,  baseline prevalence of sexual transmitted diseases).

Infertility in men's reproductive systems can result from:

  • Obstruction of the reproductive tract causing dysfunction in the ejection of semen. This blockage can occur in the tubes that carry semen (such as ejaculatory ducts and seminal vesicles). Blockages are usually due to injuries or infections of the genital tract.
  • Hormonal disorders that cause abnormalities in hormones produced by the pituitary gland, hypothalamus and testes. Hormones such as testosterone regulate sperm production. Examples of diseases that lead to hormonal imbalance are pituitary or testicular cancer.
  • Failure of the testicles to produce sperm, for example, due to varicoceles or medical treatments that affect sperm-producing cells (such as chemotherapy).
  • Abnormal sperm function and quality. Conditions or situations that cause abnormal sperm shape (morphology) and movement (motility) have a negative effect on fertility. For example, the use of anabolic steroids can lead to abnormal semen parameters such as sperm count and shape. (World Health Organisation, 2023; Gore et al. 2015)

Lifestyle factors such as smoking, excessive alcohol consumption and obesity or extreme low body mass index can increase the incidence of fertility. In addition, exposure to environmental pollutants and toxins (gonadotoxic medications) can be directly toxic to gametes (eggs and sperm), resulting in reduced numbers and poor quality.(World Health Organisation, 2023; Gore et al. 2015; Segal et al. 2019)

INFERTILITY - PATIENT PERSPECTIVE

Slide 8-9. - PERSONAL CONTEXT

The perception of Infertility is a different experience from the perspective of the woman or the couple as opposed to the medical point of view. Overall, male infertility experiences are under-investigated (Culley et al. 2013). This paragraph will discuss the topic of infertility from a  medical communication perspective. In this syllabus we will concentrate on gaining a closer understanding of the female experience of infertility. We will first focus on the possible emotions that women may experience due to their infertility. Indeed, emotions are context-dependent, but now we list them in isolation. In the literature various emotion lists related to infertility can be found. For instance, infertility often accompanies emotional responses such as feelings of failure, inadequacy, and reduced competence; a sense of isolation and alienation from those who can conceive; a profound feeling of stigma; and a strong commitment to treatment. Greil et al. (Greil et al. 2010) compile the following emotions and experiences related to fertility based on a literature review: negative identity; a sense of worthlessness and inadequacy; a feeling of lack of personal control; anger and resentment; grief and depression; anxiety and stress; lower life satisfaction; envy of other mothers; loss of the dream of co-creating; the ‘emotional roller coaster’; a sense of isolation.

On the slides, each of the listed emotions from the article is accompanied by a possible specific thought to illustrate and make tangible what a woman might experience concerning her fertility.

INFERTILITY - PATIENT PERSPECTIVE

Slide 10-15. CULTURAL CONTEXT

The experience of infertility is also influenced by personal/ social/ cultural / religious context. Factors such as socioeconomic status, religious influences, cultural beliefs, social structure, and so on can shape the experience. The following example (case 1) illustrates a case of a highly educated immigrant woman in a European fertility center:

“I am 37 years old. I came from Turkey to Austria when I was a child. I have a law degree, working as a lawyer. My husband and I live within the local Turkish community. It has been 5 years since I've been unable to get pregnant, and we can't find any objective reason for it, apart from the fact that my husband's sperm count is insufficient. But of course, as I have had long years of education, it might be that I am too old for my first child. I wouldn't want a male doctor to examine me. Only if the female doctor is here, then I would allow myself to be examined.”

The example clearly demonstrates how  social context can shape a person's experience in many ways. As part of a minority group, living within the local community brings about both a sense of separation and belonging in society. In her case, the community represents a different religious culture and perhaps even a family structure and gender roles, which are distinct from the majority society. Meanwhile, the woman is highly qualified, and based on her profession, she is also a member of another community to which she may be loyal. As it turns out, she chose her field of study herself, going against the values of her immediate environment.

The following example (case 2.) illustrates how different patient-doctor relationship perceptions could hinder cooperation
“I'm Jennifer, 27 years old, and I've been trying to have a child for 5 years. I have bilateral ovarian blockage. I weigh 95 kilograms and I smoke. I can't quit, I'm trying, maybe I'll succeed temporarily, but maybe not. Should I lose weight? Don't tell me that, I've paid this money, they should do it for me. This is the third attempt, I'm a bit frustrated, I don't even know why it's not working when I believed it would (in vitro fertilization). I'm sure the doctor is bad, they didn't check everything, they're not helping enough, I'm dissatisfied.”

The example clearly demonstrates that the woman sees herself as more of a client towards the doctor. Payment, in this case, serve as a way to remove responsibility from herself and provide a means of accountability for the other party. This patient role can be psychologically rewarding (no need to take responsibility, in case of failure there is someone to blame), but it certainly doesn't support a cooperative patient-doctor relationship.

As seen in the examples, the experience of infertility is highly influenced by the social context. Specifically, it is shaped by explicit or implicit social norms related to fertility and infertility, which can be observed in religious doctrines, folk beliefs, stigma, and gender dynamics.  Medical personnel need to be able to decipher the reactions of the treated person in order to find a common ground for an acceptable treatment method.  

Slide 16.- INFERTILITY - THE CONVERGENCE OF PERSPECTIVES

The medical perspective and the patient's perspective in the treatment of infertility not necessarily have the same approach. In this relationship, the patient is in a vulnerable position, and the doctor offers a potential solution to their problem. The patient has sought medical help because they see it as an opportunity to change their situation. However, there can still be challenges in their interaction. The communication model described here represents the medical communication approach, in which the decision about intervention is made in partnership, and after the decision, the doctor leads the intervention, while the patient cooperates (Cheng et al., 2015). Infertility treatment represents a special medical case:  as here, participative (patient-doctor) decisions of treatment options can be followed by a doctor-led interventions (in contrast e.g. to intensive therapy cases or acute infections, where medical stuff leads most of the decision-making).
However, to make a decision together, it is first necessary to build trust (pacing). The steps of pacing can be seen on the slide: recognise the other’s feelings; acknowledge them; reflect back that you accept them, validate that they are natural.

ART - MEDICAL PERSPECTIVE

Slide 17 - DEFINITION
A new era began with the birth of Louise Brown, the first newborn conceived through in vitro fertilisation (IVF), in 1978. Since then, more than 7 million babies have been born worldwide through assisted reproductive technology (ART).
All procedures that include the in vitro handling of  human oocytes and sperm or of embryos for the purpose of establishing a pregnancy fall into the category of ART.
ART does not include assisted insemination (artificial insemination) using sperm from either a woman’s partner or a sperm donor.

Slide 18-20. ADVANCEMENTS AND FORMS OF ART

Addressing infertility is an important part of realizing the right of individuals and couples to have a family.
A wide range of people around the world may need infertility management and access to fertility care services. The number of yearly performed ART cycles has risen approximately threefold in the United States, fourfold in Europe, sixfold in Japan and by at least tenfold in China. (World Health Organisation, 2023; Alon et al. 2023)

Availability, access and quality of interventions concerning infertility vary greatly among European countries and even more worldwide. Due to the fear of decreasing European population and decreasing birth rates, prevention, diagnosis and treatment of infertility are more often prioritized in national policies, but the framework of infertility care is largely influenced by cultural, religious, national, and political values. The lack of medical infrastructure and accessible public health funding pose additional barriers to universal access to fertility care. While assisted reproductive technology (ART) has been available for over three decades, its availability and affordability is different on a national level even in the European Union. (World Health Organization, 2023)

Assisted reproduction has seen significant milestones. The groundwork for assisted reproduction was laid with early experiments in the 1950s, including in vitro fertilization (IVF) in animals (Bavister, 2002).Than Louise Brown, the first "test-tube baby," was born in 1978, marking a major breakthrough in human IVF. The 1980s saw the development of Gamete Intrafallopian Transfer (GIFT), an alternative to IVF, where both egg and sperm are placed directly into the fallopian tube. Intracytoplasmic Sperm Injection (ICSI), a technique to inject a single sperm into an egg, was introduced in 1992, revolutionizing male infertility treatment. Preimplantation Genetic Diagnosis (PGD)became available in the late 1990s, allowing for the screening of embryos for genetic disorders before implantation. The 21st century has witnessed significant advances in egg freezing technology, expanding options for fertility preservation and family building.The donation of germ cells (sperm and eggs) and embryos as well as surrogate motherhood are controversial topics.

Slide 21-27 - Treatment
After evaluating the reasons for infertility, there is a wide range of Infertility treatment methods, which can be utilized. Before turning to ART methods with young, healthy, couples with patent tubes and good sperm count, cycle monitoring and timed intercourse might be the first step.
Slide 22
Insemination might improve outcome if intercourse not possible and the sperm count is good and tubes are open.
Sperm count
In addition to clarifying the woman's condition, a spermiogram is mandatory as part of fertility treatment. This must be carried out in accordance with WHO standards and must be performed before any invasive diagnostics of the woman or before the start of treatment. Even if the man has already fathered children in the past, it cannot be concluded that the spermiogram is normal and a spermiogram check is also required. Certain parameters are looked at to interpret the sperm count.
- Volume ≥1.5ml
- Concentration ≥15 million sperm /ml
- Progressive motility ≥32% (category a+b)
- Morphology normal forms ≥ 4%

With regard to motility, the following 4 categories are distinguished:
a.    Fast progressive motility
b.    Slowly progressive motility
c.    Local motility
d.    Immotility

The following definitions were established on the basis of the above-mentioned parameters:
- Normozoospermia: an unremarkable spermiogram in all parameters
- Oligozoospermia: reduced concentration
- Asthenozoospermia: progressive motility <32%
- Teratozoospermia: proportion of normally formed sperm <4%
- Azoospermia: no sperm in the ejaculate
- Aspermia: no ejaculate

Slides 23-27
Historically, the first IVF treatments utilized the changes of a spontaneous cycle, with only one egg being retrieved. Further studies have shown that it is possible to induce ovulation by administering gonadotropins during the menstrual cycle in order to obtain a larger number of eggs, which largely changed the effectiveness of this process. Numerous stimulation protocols have been introduced for controlled ovarian hyperstimulation in patients undergoing in vitro fertilization treatment.
One of the most pivotal developments has been In vitro Fertilization (IVF), a process where eggs and sperm are fertilized in a laboratory setting before being implanted into the uterus. IVF has brought hope to countless couples struggling with infertility.
Intracytoplasmic Sperm Injection (ICSI) is another notable breakthrough, allowing the direct injection of a single sperm into an egg. This technique has revolutionized the treatment of male infertility cases and increased the chances of successful conception.
Advances in genetic testing have also played a crucial role. Preimplantation Genetic Diagnosis (PGD) enables the screening of embryos for genetic disorders before implantation, reducing the risk of inherited diseases. Preimplantation Genetic Screening (PGS) further enhances this process by screening embryos for chromosomal abnormalities, in some cases improving the odds of a successful pregnancy.
Egg donation, sperm donation, and embryo donation have opened new avenues for individuals and couples facing fertility challenges.

Slide 28. - Modifiable and non- modifiable factors influencing ART outcome

Most ART treatments are carried out on women between the ages of 30 and 39. Young and healthy normal weight women under 35 years of age have 25-35% chance of a live birth after conception with assisted reproductive technologies. This success rate might be improved in the concomitant cycles. Women over 35 years of age have a decreased success rate. Age is the major factor, which influences ART success.  ART outcome is also  influenced by modifiable factors such as "Patient related parameters" and "clinical practices." Patient-related parameters, like lifestyle choices and health behaviors, can be modified to enhance treatment success. BMI being one of the most important modifiable parameters. On the other hand, "uncontrollable aspects" and "laboratory aspects," categorized as non-modifiable factors, encompass elements beyond patient or clinical control, emphasizing the significance of optimizing modifiable factors within the constraints of these uncontrollable elements to improve ART outcomes.
The medical process of ART often starts with serial hormone injections, in the frame of controlled ovarian stimulation. This is followed by follicle puncture, which is an invasive method to retrieve eggs, which in turn will be fertilized either through IVF process of ICSI. If fertilization occurs, embryos will develop to a blastocyst stage and will be transferred into the uterus. Two weeks later pregnancy can be detected with a pregnancy test.
There are many stages of this process, where treatment failure and emotional disappointment (from the patient and medical personal)  might occur. Patients need to meet certain characteristics to be able to be stimulated (patients who suffer from premature ovarian insufficiency or patients with advanced age) might not reach these conditions to begin with the stimulation process. Follicles might not develop, eggs might not be harvested, eggs might not be fertilized, embryos might not develop sufficiently (poor embryo quality), the endometrium might not be sufficient for a transfer, pregnancy might not be reached, early abortion, extrauterine gravidity might occure.  This process  is described in an accompanying short video.  

ART - PATIENT PERSPECTIVE

Slide 29 - PERSONAL CONTEXT

Experiencing infertility alone elicits mixed emotions. When a couple decides to undergo any type of infertility treatment, inevitably, new emotional impacts occur: from hope to the experience of a significant loss or failure.  A survey conducted in 2002 (Verhaak et al. 2002) included 240 women and 219 men who were questioned both before and after their first intrauterine insemination. Specifically, their levels of anxiety and depression, their sexual life, and their plans related to further interventions were the focus of the study.
They found that:
 “After a first failed treatment cycle, both women and men showed an increase in depression, while women also showed increased anxiety.”
“After the first failed cycle, almost 13% of the women showed clinically relevant forms of depression.”
“There was an increase in dissatisfaction with the sexual relationship in both men and women regardless of the success of the treatment.”
There are already data available for detailed tracking of changes in the emotional states of couples during the process (Gabnai-Nagy, 2021). In summary, it seems advisable to accompany the entire process with expert psychological support (Frederiksen et al 2015, Peterson and Eifert 2011).
As it could be seen, infertility and ART are bio-psycho-social problems. An approach only in medical terms neglect behavioral aspects and psychosocial implications of the topic. Infertility itself and treatment are stressors and have a huge impact on wellbeing and quality of life: The longer the  period of depression, and anxiety (both partners) the higher is the incidence of somatic symptoms (women).
Slide 30 - 32. - Psychological Support for ART Patients

Psychological support aims not to improve the success rate of the treatment.   There is no evidence that psychological interventions could influence the rate of pregnancies. The aim of psychological counseling regarding infertility and ART could be the reduction of stress related to infertility and its treatment; exploring alternatives; providing emotional support; and delving into infertility-related (unconscious) emotions, beliefs, and thoughts. Involving psychological counseling in ART and infertility treatment should be standard practice, especially at the diagnosis of infertility, with patients struggling with addictions, eating disorders (even subclinical cases), behavior patterns that reduce fertility, decisions about the type of treatment, during the IVF cycle, when treatments end without pregnancy, during miscarriage, at the end of treatment, always before gamete donation, and when requested by a patient.

Slide 33 - 34.
ART - THE CONVERGENCE OF PERSPECTIVES

ART is a challenging process where the doctor needs to lead the patient (guidance-cooperation model). To start, it is important for the doctor and the woman/ the couple to make the decision together (mutual participation) (Cheng et al, 2015). Making decisions among the different treatment options requires a clear presentation of the situation and the options, followed by recognizing and accepting cultural, ideological, emotional etc. differences. The decision-making process may not always align with the doctor's convictions. It is crucial to accept the emerging feelings. After the decision finding, the doctor's role is to lead the woman or the couple on the path of cooperation.

Slide 35 - 36.  Controversial Topics of ART

Assisted Reproductive Technology (ART) presents a complex landscape where the patient's perspective is of paramount importance. This intricate world is deeply influenced by cultural context, introducing ethical issues that span a wide spectrum of concerns.
One of the basics of ethical issues of ART lies in the dilemma of Embryo Disposition, which involves pivotal questions such as how many embryos to transfer and the fate of surplus embryos. These decisions encapsulate the hopes for successful pregnancies while raising ethical concerns about what happens to the remaining embryos.
Exploitation is also a pressing ethical issue, with apprehensions about the potential exploitation of donors, surrogates, and vulnerable populations involved in the ART process. The delicate balance between medical advancements and ethical considerations is crucial to protect the rights and well-being of all involved. Eugenics and Designer Babies emerge as subjects of ethical concern, as they touch upon the selection of specific genetic traits in embryos and the potential for creating "designer babies.

The legal landscape surrounding ART is multifaceted, encompassing issues among many related to child welfare, embryo disposition, social egg freezing, reproductive tourism, and gender selection. Legal matters delve into the welfare and rights of children born through ART, the disposition of surplus embryos, egg freezing and usage, reproductive services across borders, and gender selection for non-medical reasons. Navigating these complexities requires a sensitive and thoughtful approach put into  personal and cultural context, one that upholds ethical standards and safeguards the rights and dignity of those embarking on the intricate journey of Assisted Reproductive Technology.

Bibliography

Alon, I., Chebance, Z., Massucci, F. A., Bounartzi, T. & Ravitsky, V. (2023) Mapping ethical, legal, & social implications (ELSI) of assisted reproductive technologies. J Assist Reprod Genet doi:10.1007/s10815-023-02854-4.

Bavister, B. D. (2002). Early history of in vitro fertilization. REPRODUCTION-CAMBRIDGE-, 124(2), 181-196.

Brezina, P. R., & Zhao, Y. (2012). The Ethical, Legal, and Social Issues Impacted by Modern Assisted Reproductive Technologies. Obstetrics and Gynecology International, 2012, 1–7. https://doi.org/10.1155/2012/686253

Cheng, B. S., Bridges, S. M., Yiu, C. K., & McGrath, C. P. (2015). A review of communication models and frameworks in a healthcare context. Dental Update, 42(2), 185–193. doi:10.12968/denu.2015.42.2.185

Culley, L., Hudson, N., & Lohan, M. (2013). Where are all the men? The marginalization of men in social scientific research on infertility. Reproductive BioMedicine Online, 27(3), 225–235. https://doi.org/10.1016/j.rbmo.2013.06.009

Frederiksen, Y., Farver-Vestergaard, I., Skovgard, N. G., Ingerslev, H. J., & Zachariae, R. (2015). Efficacy of psychosocial interventions for psychological and pregnancy outcomes in infertile women and men: A systematic review and meta-analysis. BMJ Open, 5(1), e006592–e006592. https://doi.org/10.1136/bmjopen-2014-006592

Gelbaya, T. A., Potdar, N., Jeve, Y. B. & Nardo, L. G. (2014) Definition and Epidemiology of Unexplained Infertility. www.obgynsurvey.com.

Gore, A. C. et al. EDC-2: (2015) The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocrine Reviews vol. 36 1–150 Preprint at https://doi.org/10.1210/er.2015-1010.

Iordăchescu, D. A., Golu, F. T., Paica, C. I., Gorbănescu, A., Panaitescu, A. M., Gică, C., Peltecu, G., & Gică, N. (2021). The Relationship between the Infertility Specialist and the Patient during the COVID-19 Pandemic. Healthcare, 9(12), 1649. https://doi.org/10.3390/healthcare9121649

Mascarenhas, M. N., Flaxman, S. R., Boerma, T., Vanderpoel, S. & Stevens, G. A. (2012) National, Regional, and Global Trends in Infertility Prevalence Since 1990: A Systematic Analysis of 277 Health Surveys. PLoS Med 9.

Miles, L. M., Keitel, M., Jackson, M., Harris, A., & Licciardi, F. (2009). Predictors of distress in women being treated for infertility. Journal of Reproductive and Infant Psychology, 27(3), 238–257. https://doi.org/10.1080/02646830802350880

Segal, T. R. & Giudice, L. C. (2019) Before the beginning: environmental exposures and reproductive and obstetrical outcomes. Fertility and Sterility vol. 112 613–621 Preprint at https://doi.org/10.1016/j.fertnstert.2019.08.001.

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Additional Reading

Helene Mitchell, Wendy Norton, Chapter 37 - Psychological impact of infertility and ART procedures, Editor(s): Antonio Simone Laganà, Antonino Guglielmino, Management of Infertility, Academic Press, 2023, Pages 387-395,ISBN9780323899079, https://doi.org/10.1016/B978-0-323-89907-9.00020-X.

Marcia C. Inhorn: Right to assisted reproductive technology: Overcoming infertility in low-resource countries, International Journal of Gynecology &amp; Obstetrics, Volume 106, Issue 2, 2009, Pages 172-174, ISSN 0020-7292, https://doi.org/10.1016/j.ijgo.2009.03.034.
  (https://www.sciencedirect.com/science/article/pii/S0020729209001556)

Natalibeth Barrera, Temidayo S Omolaoye, Stefan S Du Plessis, Chapter 6 - A contemporary view on global fertility, infertility, and assisted reproductive techniques, Editor(s): Diana Vaamonde, Anthony C. Hackney, Juan Manuel Garcia-Manso, Fertility, Pregnancy, and Wellness, Elsevier, 2022, Pages 93-120,ISBN9780128183090, https://doi.org/10.1016/B978-0-12-818309-0.00009-5.

Susan Gitlin, Alys Einion, Chapter 25 - Ethics in fertility and pregnancy management, Editor(s): Diana Vaamonde, Anthony C. Hackney, Juan Manuel Garcia-Manso, Fertility, Pregnancy, and Wellness, Elsevier, 2022, Pages 479-492,ISBN9780128183090, https://doi.org/10.1016/B978-0-12-818309-0.00015-0.

Shereen Assaysh-Öberg, Catrin Borneskog, Elin Ternström: Women’s experience of infertility & treatment – A silent grief and failed care and support, Sexual Reproductive Healthcare, Volume 37, 2023, 100879, ISSN 1877-5756, https://doi.org/10.1016/j.srhc.2023.100879. (https://www.sciencedirect.com/science/article/pii/S1877575623000691)

ART fact sheet. https://www.icmartivf.org/reports-publications.
Factsheet on infertility-prevalence, treatment and fertility decline in Europe. (2021).

Mikwar, M., MacFarlane, A. J. & Marchetti, F.  (2020) Mechanisms of oocyte aneuploidy associated with advanced maternal age. Mutation Research - Reviews in Mutation Research vol. 785 Preprint at https://doi.org/10.1016/j.mrrev.2020.108320.

Gourinat, A., Mazeaud, C., Hubert, J., Eschwege, P. & Koscinski, I. (2023) Impact of paternal age on assisted reproductive technology outcomes and offspring health: a systematic review. Andrology Preprint at https://doi.org/10.1111/andr.13385.

Siegl V. 2023, Intimate Strangers: Commercial surrogacy in Russia and Ukraine and the making of the truth, (2023) Cornell University Press ithaca and London. ISBN 9781501771316 (paperback) or 9781501769948 (epub)

Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the Foundation for the Development of the Education System. Neither the European Union nor entity providing the grant can be held responsible for them.