Evaluate How Advances Reproductive Technology Promote Human Fertility Biology Essay

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Experts define infertility as not being able to conceive after at least one year of trying. Women who are able to conceive but then have difficulties carrying the baby, having repeated miscarriages are also said to be infertile.

In order to get pregnant a woman must go through an ovarian cycle, this happens after the onset of puberty, the ovary consistently alternates between two phases, the foliicular phase, which is dominated by the presence of maturing follicles, and the luteal phase which is characterised by the presence of the corpus luteum (Sherwood 2010). Normally this cycle is interrupted only if pregnancy occurs and is finally terminated by menopause. The average ovarian cycle is 28 days long, but varies amongst women. Around 12% of women (7.3 million) in the United States aged 15-44 had difficulty conceiving or carrying a baby to term in 2002, according to the National Centre for Control and Prevention.(Infertility.com 2010)

Female infertility can be caused by a range of problems, sex-hormone abnormalities, low-thyroid function, endometriosis, scarring of the fallopian tubes connecting the ovaries with the uterus or a host of other factors. For most infertile women, no symptoms accompany the infertility. Some women with symptoms of obesity, acne and excessive facial hair, heavy, irregular, absent menstrual periods, or fluid leaking from the breasts could have hormone imbalances that might interfere with fertility.

Over recent years, the average age of patients seeking infertility treatment has increased. Since the development of effective contraception in the 1960s, women have been able to delay childbearing , and the average maternal age increased by approximately 5 years between the periods 1965-1969 and 1995-1999. The tendency towards deferred childbirth has also risen steadily since assisted reproductive technology (ART) treatments for infertility became available in 1980. After approximately 30 years of age, fertility decreases with increasing age, with a slow but steady decline in fertility in women aged between 30 and 35 years, which is followed by an accelerated decline. Data from the 16th to the early 19th century show that women who married late were more likely to die childless; women who married when more than 35 years of age had twice the chance of dying childless compared with those who married when aged 30-34 years. Thus, delayed childbearing reduces the chance of achieving a spontaneous pregnancy.

A combination of delayed childbearing and reduced natural fecundity with increasing age has resulted in a steady increase in the number and proportion of women aged ≥35 years who are seeking ART treatment. Unfortunately, the outcomes of treatment with ART are also adversely affected by advanced patient age, and it is becoming increasingly important to optimize treatment outcomes for these older patients.

Although chronological age is the most important predictor of ovarian response to follicle-stimulating hormone (FSH), the rate of reproductive ageing varies considerably among individuals. Both environmental and genetic factors contribute to biological ovarian ageing. Thus, chronological and biological age are not always equivalent. (Alviggi et al 2009)

Assisted Reproductive technologies, ART, are defined primarily by the first procedure that was developed, which was In Vitro fertilisation and embryo transfer, IVF, is the removal of the human oocyte from the ovary. Fertilization by sperm in the laboratory, then transfer of the embryo back into the uterus. Gamete intrafallopian transfer (GIFT) and Zygote intrafallopian transfer (ZIFT) are derivatives of IVF. GIFT is the removal of the oocyte from the ovary, but instead of fertilisation outside the body (In Vitro), the egg and sperm are mixed together, placed into the fallopian tube, where fertilization and embryo development takes place. In ZIFT, the egg is removed and fertilized in the laboratory. The fertilized egg at the pronuclear stage is then placed into the fallopian tube hoping that the tubal environment, just as in GIFT, will aid in embryo development, growth and preganancy.(IVF, GIFT, ZIFT) IVF, GIFT, ZIFT, and TET are very similar procedures although there are a few significant differences. During IVF-ET, ZIFT, and TET, the oocytes and sperm are combined in a culture dish in the laboratory. Fertilization and very early embryo development occur outside the body, rather than in the fallopian tube. Once early embryo development is recognized, the embryos are transferred either into the uterus (IVF-ET) or the fallopian tube (ZIFT, TET). Since most programs have seen no significant difference in success rates, they usually perform IVF-ET because it is less expensive and doesn't require laparoscopy and general anesthesia. In addition, IVF-ET is the only procedure available for women with damaged fallopian tubes. (SART 2009)

Picture below is of ZIFT .

GIFT differs from the other procedures in that sperm and oocytes are transferred into the fallopian tubes immediately after oocyte retrieval. Fertilization thus occurs in the body, rather than in the laboratory. GIFT originally was thought to represent a breakthrough in infertility therapy. National ART statistics suggest that success rates are higher with GIFT than IVF-ET. However, many investigators have concluded that GIFT does not increase the likelihood of conception compared to other ART procedures, and that the statistics may reflect differences in laboratory expertise or in the kinds of patients treated with GIFT versus IVF-ET. In addition, GIFT does not allow for confirmation of successful fertilization if the procedure does not produce a pregnancy. Because of these disadvantages, most programs do not perform GIFT.

Picture below shows GIFT.

Picture below shows IVF.

"IVF is now commonplace. Routine egg freezingÂ-and more pregnancies deferred till middle ageÂ-will happen sooner rather than later. Gay men becoming dads by using surrogates is already last year's outrage, while mothers in their sixties are increasingly tolerated. Even ovaries grafted to unusual places could end up providing genuine ovulation. Are there any technical, or even ethical, limits? It's hard to be sure, at least if major scientific conferences are anything to go by. Nor is the public showing any signs of losing its appetite for assisted reproductive technology" (New Scientist 2000)

On July 25th 1978, Louise Joy Brown, the worlds first successful "test-tube" baby was born in Great Britain. Though the technology that made her conception possible was heralded as a triumph in medicine and science, it also caused many to consider the possibilities of future ill use. (Human Fertilisation and Embryology Authority, 2009e)

Advantages in ART have revolutionised the management and care of couples facing infertility or increased risks for genetic conditions. Most recently, an application of ART has included the option of family balancing, or increasing the chance of having a child of a particular gender due to family history of a sex-linked genetic disease or the under representation of a gender within one family.

As the incidence and awareness of infertility has risen in the last decades, reproductive endochronologists and scientists have striven to improve the therapeutic options being offered to patients.

As the fertility treatment has become more effective and widely available, there has been a steady increase in the number of multiple births. It is generally been viewed that multiple births and specifically those resulting from assisted reproduction, are to be avoided. This is because of the well documented risks to children, such as pre-term birth and low birth weights and the associated increased possibility of physical disability and learning difficulties. It is also thought that the rate of cerebral palsy is increased in multiple births as compared to single births.(Berry 2004)

Multifoetal pregnancy reduction (MFPR) refers to the termination of one or more presumably healthy foetuses in a pregnancy containing three or more foetuses (Berkowitz 1996). There are many risks associated with high-order pregnancies, both for the mother and the babies (SHER 2006). Termination of one or more foetuses aims to reduce these risks. This poses ethical dilemmas however, in terms of whether it is acceptable to sacrifice some foetuses for the sake of others (Birkowitz 1996). The higher the number of foetuses a mother carries directly increases her risks of hypertension, haemorrhage and the need for a caesarean delivery (SHER 2006) (ACOG 2004). The children are more likely to be born premature and to have physical and neurological problems (SHER 2006) (ACOG 2004) (Kumar 2004). There is also an increased chance of maternal and foetal mortality (Birkowitz 1996) (ACOG 2004). For all these reasons it is believed that MFPR is justified in terms of beneficence, as it would reduce the risks of morbidity and mortality (Chervanak 1999). It has been argued however, that there are medical risks posed to the remaining foetuses by the reduction procedure (ACOG 2004) (Chervanak 1999). The remaining babies tend to be of a lower birth weight and are at a higher risk of prematurity (Chevanak 1999) (Fleming 1997). The procedure carries the risk of losing all the foetuses through miscarriage (Fleming 1997). The main ethical problem with MFPR is that it involves the intentional sacrifice of healthy foetuses to save the others (ACOG 2004). The ethical principle of justice requires that all the foetuses are treated equally, so intentionally killing innocent human beings- even if the outcome would be positive for the surviving babies- cannot be justified (ACOG 2004) (Fleming 1997) (Pinchuk 2000).

Proponents of MFPR claim that it is justified when the risks of carrying a Proponents of MFPR claim that it is justified when the risks of carrying a pregnancy are considerable, and could be reduced if there were fewer foetuses (ACOG 2004). The primary intention of reduction is not to end life, but to improve the chances of survival of the remaining foetuses (ESHRE 2003).

In humans, the three major outcomes of ART are no pregnancy, a single pregnancyand a multiple birth pregnancy. Multiple gestations (whether twins, triplets or higher multiples) are associated with high healthcare costs and considerable morbidity and mortality for both the newborns (often premature) and the mother, as well as with additional unexpected financial stress on the parents. To reduce these adverse sequelae of ART, reproductive societies and countries have adopted guidelines to promote single-embryo transfers, especially in women younger than 35 years old.

Another factor that is effected by ART is the psychological welfare of the couple involved in treatment and can be quite demanding over an extended period of time, ranging from initial speculation of fertility problems, anticipation in the time elapsed between diagnostic tests and receiving results, the results themselves and discussion of treatment options after diagnosis. Rashidi et al (2008) conducted a study on the psychological well being of couples who were undergoing IVF or ICSI treatment. The study showed that women suffer greater adverse psychological effects than men. It also showed that the cause and duration of infertility were not significant factors. Significant factors included the age and the educational level of women, younger less educated woman suffered greater psychological effects. Also the study found that physical and mental health were significant indicators of adverse psychological effects caused by to infertility treatments.

One controversial ethical and legal consideration relevant to the use of reproductive technologies is the possibility that the use of those technologies harms the children they are used to create. And at the heart of the question of whether or not those future children can be harmed by the use of such technology is the concept of identity. Many ethicists have argued that it is incoherent to claim that a child can be harmed by an intervention that she owes her very existence to, because the use of that technology changes the identity of the child brought into the world. (Malek 2006) Perhaps one of the most contentious proposed applications of pre-implantation genetic diagnosis or PGD is to create "designer babies", that is children who are selected for specific desired traits (Hensley 2004). There are medical reasons for using PGD in this way, to create "saviour siblings" that can donate life-saving tissue to an existing child . Conditions such as thalassaemias, leukaemias and rare anaemias can be fatal if untreated , and for many sufferers the only cure is stem cell or bone marrow donation from a person who is a tissue match. PGD allows a sibling who will provide such a match to be chosen for the existing child (Robertson 2003). Therefore saviour siblings are clearly beneficial as they can save the lives of existing children and PGD for that purpose gives families a controlled way of obtaining a sibling donor (Sheldon 2004).

Recently, a series of reports have raised concern about a possible relation between assisted reproduction technologies (ART) and genomic imprinting disorders (Chang et al., 2005; Cox et al., 2002; Gosden et al., 2003; Horsthemke and Ludwig, 2005; Ludwig et al., 2005; Maher et al., 2003; Maher, 2005; Sutcliffe et al., 2006). For years it has been known that IVF and embryo culture can affect the methylation status of some genes in mice, cattle and sheep, and it was postulated to happen in humans as well (Ceelen and Vermeiden, 2001; Horsthemke and Ludwig et al., 2005). This raised the issue of a possible increased risk in ART for conceiving a child

with disorders that can be caused by a disturbed imprinting, such as Beckwith-Wiedemann syndrome (BWS) and Angelman syndrome (AS) (Maher, 2005).

(Doornbos 2007)

ART provides so many couples with the chance to be borne a child , but at what cost does it come physically, mentally and financially? Couples who are considering ART should realize that it is an intensely emotional, physically arduous, and expensive procedure. Most couples find it difficult to consider the chances for success realistically without dampening the drive that allows them to undertake these procedures. Above all, couples should explore plans for the future, whether or not their attempts at ART are successful.

What does all this mean in terms of social policy? It is clear that a greater proportion of social resources should be redirected to broader programs that will reduce the incidence of health problems, including infertility. It is also clear that the new technologies need to be regulated to ensure insofar as possible that their benefits outweigh their potential harms, and that such regulation must be sensitive to the often discounted interests of members of disadvantaged groups.(Purdy 1996)

The greatest challenge posed by the research successes realized to date and in the future will be the translation of the research findings in both mouse models and in human male infertility into clinical practice. Indeed, the literature is replete with hundreds of papers reporting a lack of success in finding mutations in infertile humans by using known mouse infertility genes as a basis for the search. In some cases, this reflects broad study subject selection criteria without rigorous classification of study groups, but more often these failures of clinical translation reflect the complexity of the signaling pathways in combination with the multitude of gene products required for each step of gametogenesis. In contrast, current clinical evaluation of infertile couples is relatively simple and superficial. After a history and physical examination, circulating hormone levels are assessed, semen analyses are performed and a genetic evaluation (if it is performed at all) is restricted to the current limits of clinical testing: a karyotype and perhaps a Y chromosome microdeletion test or a test for sperm aneuploidy (for the males). The diagnoses are usually descriptive of the observed problem, with no mechanistic insight into etiology. With the development of ART, many otherwise hopelessly infertile couples can experience parenthood. It is our expectation that someday, the research advances of today can be used to cure infertility, in contrast to the current practice of overcoming infertility using defective gametes, and at the same time ensure the birth of a healthy baby for all couples desiring parenthood.(Matzuk 2008)

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