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Who should have in vitro fertilization treatment?

Patient selection for ART remains a vexed question that is hotly de­bated. IVF is costly, carries a small but real risk of harm, and there are anxieties about the long-term health of children born after ART, although these remain largely theoretical.

The most significant de­terminant of success in IVF is the age of the woman so while it may be prudent to promote a conservative policy of access to ART in cases where there is no clear diagnosis for the infertility problem and where the couple are young, a more rapid referral is probably a better option when the woman is approaching or beyond her 35th birthday. There are many powerful social pressures on couples to conceive a child at a certain time in their lives: pressure from younger siblings and friends who are having their children, pressure from parents who wish to be grandparents, and the pressure of the ‘biological clock' that is discussed on a daily basis in the popular press. Hence, a consultation concerning ART should always be a negotiation with the couple, respecting their desire to use ART to start their family as quickly as possible while using population-based statistics to help to reach a mutually agreed and medically sensible plan.

Alternative approaches to IVF should always be considered. Many couples have religious or moral objections to the IVF process, par­ticularly if embryo freezing is to be used, and may only consent to an attenuated form of treatment with, for example, fertilization of only one or two oocytes to avoid the possibility of there being super­numerary frozen embryos later. Alternatives that may be applicable to defined diagnostic categories include ovulation induction with oral or injectable agents, ovarian diathermy, intrauterine insemin­ation, or tubal or other reproductive surgery. However, as IVF has become more widely used it has become the dominant form of treat­ment for most categories of infertility and is a widely used approach to ‘unexplained' infertility as it can reveal problems of poor ovarian reserve, failure of sperm to fertilize the oocyte, or poor embryo de­velopment that cannot easily be tested outside of an IVF cycle.

Table 52.1 Some significant developments in ART

1980 2017
Natural cycle to obtain one oocyte Stimulated cycle to obtain multiple oocytes
Multiple blood tests to monitor natural ovulation Transvaginal ultrasound with minimal blood tests
Lack of control over timing of ovulation Pituitary downregulation or GnRH antagonist to suppress premature ovulation
Laparoscopic oocyte collection with general anaesthesia Transvaginal ultrasound-guided egg collection with sedation
Simple culture medium, rudimentary incubators Stage-specific culture media, sophisticated control of temperature, humidity, gases
Incubation with sperm Intracytoplasmic sperm injection for male infertility
Embryo transfer 2 days after egg collection Extended culture to day 5 blastocyst
Operator-blind embryo transfer Ultrasound-guided embryo transfer
Natural cycle transfer Luteal support with progestogens or hCG
One attempt, one oocyte Multiple oocytes allowing for embryo freezing and later replacement of frozen embryo
Multiple embryo transfer, high rates of multiple pregnancy Single embryo transfer with option for later frozen embryo transfer
Fresh embryo transfer with abnormally stimulated endometrium 'Freeze all' embryo policy with natural cycle transfer for regularly ovulating women
Embryo selection by simple morphological criteria Video time-lapse and embryo biopsy/ PGS for embryo selection
Significant risk of ovarian hyperstimulation syndrome (OHSS) GnRH antagonist-controlled superovulation with agonist trigger and 'freeze all' embryos removing risk of severe OHSS

Social changes have led to considerable adjustment in the case mix seen by clinics in the Western world. There has been a wide­spread trend towards deferring attempts to start a family such that the mean age of the woman at first birth is now over 30 years in many developed countries.

This has in turn led to an increase in ‘unex­plained’ infertility caused by poor oocyte quality with an increase in the proportion of aneuploid embryos and also decreases in quality and number of mitochondria in the oocyte. Advancing female age is also associated with an increase in rates of miscarriage and chromo­somal abnormality in offspring (3) (Figure 52.1). Male infertility has also appeared to increase over the last three decades, possibly mainly due to environmental factors and lifestyle factors such as obesity, smoking, and use of recreational drugs including alcohol (4). The global increase in obesity has also contributed to an increase in the number of women who are found to be anovular with polycystic ovary syndrome (5).

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Source: Arulkumaran S., Ledger W., Denny L., Doumouchtsis S. (eds.). Oxford Textbook of Obstetrics and Gynaecology. Oxford University Press,2020. — 928 p.. 2020
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