BIOLOGY Volume 3 - A Guide to General Biology - 2004

21. REPRODUCTION

21.9. Human Intervention in Reproduction

21.9.4. Treatment of Infertility

In cases where the causes of infertility are linked to factors such as smoking, obesity, or stress, Treatment should focus on eliminating or mitigating these specific factors. Surgical and hormonal interventions were discussed earlier in the sections dedicated to specific types of infertility (see also Fig. 21.57). In addition, there are several other Methods available, including In vitro Fertilization and Artificial Insemination using donor sperm.

In Vitro Fertilization (IVF)

This method is commonly known as the "test-tube baby" technique. It was first developed by Patrick Steptoe and Robert Edwards in 1978 to help women with blocked Fallopian tubes. Today, the method is considered highly effective and is widely used for patients with damaged tubes. IVF is also utilized in cases of Endometriosis, low sperm count, or abnormal sperm (since fewer sperm are required for in vitro fertilization of egg Cells), as well as when either the man or the woman produces anti-sperm Antibodies. If a woman is unable to produce her own eggs, IVF makes it possible to use donor eggs (see below).

The IVF Procedure involves fertilizing one or more egg cells outside the body and subsequently transferring these cells, referred to as "early embryos," back into the Uterus — a stage known as "embryo transfer." The entire process consists of the following steps: 1) hormonal stimulation of the Ovaries to yield multiple eggs; 2) retrieval of mature eggs; 3) laboratory fertilization of the eggs; 4) Maintenance of the early embryos in tissue culture; and 5) embryo transfer into the uterus.

OVARIAN STIMULATION. The ovaries are stimulated with FSH-containing medications to produce multiple eggs, thereby increasing the chances of successful retrieval and fertilization. Clomiphene can also be used to stimulate ovulation. These drugs should be administered at the beginning of the Menstrual cycle. Follicular growth is monitored using ultrasound scanning, which makes it possible to determine the number and size of the follicles. Blood tests for estrogen, progesterone, or LH help pinpoint the approach of ovulation. An injection of human chorionic gonadotropin (a hormone very similar to LH) can help control the timing of ovulation more precisely.

EGG RETRIEVAL. Eggs can be retrieved from the follicles via laparoscopy. A laparoscope is a telescope a few centimeters long that is inserted into the Abdominal cavity, usually through the navel, to examine the pelvic region where the ovaries, Fallopian tubes, and uterus are located. Carbon dioxide gas is introduced into the abdominal cavity to expand it and separate the body wall from the intestines. This procedure is performed under general anesthesia. The bright light emanating from the laparoscope allows the surgeon to clearly view the internal structures. Eggs are retrieved by aspirating the fluid contents of mature follicles using a fine hollow needle, also inserted through the abdominal wall. The aspirated fluid is immediately examined under a Microscope, and any eggs found are transferred to a special culture medium and placed in an incubator maintained at body Temperature. Typically, 5 to 15 eggs are successfully obtained.

As an alternative approach, eggs can be retrieved from the Fallopian tubes transvaginally, guided by ultrasound imaging. This method does not require general anesthesia, although pain relievers and sedatives are administered.

FERTILIZATION. Sperm is collected from the male partner and washed in a culture medium to remove the seminal fluid. Approximately 6 hours after the eggs are retrieved, sperm is added to them at a ratio of 100,000 sperm per single egg Cell. This procedure is carried out in a Glass Petri dish or test tube. The fertilized eggs are left in the culture medium for about two days, during which time they typically reach the 2- to 8-cell stage. They are examined under a microscope to ensure they are suitable for transfer into the woman's uterus. The more eggs transferred to the uterus, the higher the chance of success; however, one must keep in mind the necessity of avoiding multiple pregnancies, especially The Development of triplets or more. Currently, it is recommended to transfer a maximum of three embryos into the uterus. The remaining ones can be frozen and stored for future attempts if needed. When three early embryos are implanted, the risk of a twin Pregnancy is approximately 23%, and for triplets, about 5%.

EMBRYO TRANSFER. The embryos are transferred in a drop of culture fluid through the cervix into the uterus using a thin plastic catheter. The fluid is gently injected into the uterus using a syringe. After a short rest (from 10 minutes to 4 hours), the woman can leave the hospital and resume a normal life, although she is usually advised to avoid strenuous activity for a few days. A pregnancy test is typically performed 14 days after the procedure.

SUCCESS RATES. When a single early embryo is transferred, the success rate is approximately 10%, for two it is 14%, and for three it is 25%. The probability of success declines significantly with age. Most clinics consider 3 to 4 attempts reasonable, but the procedure is so emotionally draining that some couples choose to abandon further attempts after a failure.

ETHICAL ASPECTS. IVF raises A number of ethical as well as broader social issues. These issues are briefly outlined below, though they undoubtedly deserve a more thorough Structure/133.html">Discussion.

1. Some individuals, based on religious and moral convictions, object to any interventions in human reproduction and, in particular, to extracorporeal fertilization.

2. The Fate of unused early embryos poses a serious ethical and moral dilemma. The same arguments regarding the right to life of early embryos, as discussed in Section 21.9.2 in the context of abortion, can be raised here. Do doctors have the right to dispose of early embryos at their own discretion? Or does this right belong to the parents? According to estimates, at least half of all naturally conceived human embryos fail to implant and are lost during the subsequent menstruation. Furthermore, During the first 14 days, an embryo can divide at any moment to give rise to identical twins, which suggests that a unique individuality cannot be spoken of prior to this point. Can remaining early embryos be used for scientific research? Currently, it is considered acceptable to conduct experiments on early embryos up to 14 days post-fertilization, since Nervous system formation has not yet begun and no Organs have yet formed by this stage. Parents may choose to have early embryos cryopreserved for future IVF cycles or to act as Donors.

3. Does freezing cause any harm to the embryos? To date, there is no conclusive evidence to suggest that it does.

4. Embryo research enables scientists to continue improving IVF techniques. Early embryos can also be used to study infertility in general, Contraception, the causes of spontaneous miscarriages, and Genetic Disorders.

5. It will soon become possible to perform extensive genetic screening on early embryos. Will this prove to be a benefit that allows us to reduce the incidence of Hereditary diseases, or will it foster a society less tolerant of genetic disorders and disabilities? Might it push us toward selecting early embryos based on specific traits, such as sex?

6. IVF is associated with an increased likelihood of multiple pregnancies, which elevate the risk of spontaneous Miscarriage and perinatal mortality. Multiple births also increase household expenses and the labor required for childcare.

7. IVF increases the risk of Ectopic Pregnancy (5% compared to 1% in the general UK population). This is linked to the frequent application of IVF in women with damaged Fallopian tubes.

8. IVF is accompanied by extreme emotional and psychological stress. Given the intense desire for success, The rate of failure is relatively high. Couples should thoroughly consult with specialists before undergoing this procedure.

9. IVF is an expensive procedure; in the early 1990s, it cost approximately £1,000–£2,000 in the UK. Couples desperately wanting children may make financial sacrifices they can ill afford. It is sometimes difficult to determine whether individuals should truly be recommended for this procedure; clinics must avoid placing their commercial interests above the welfare of the patients seeking their help.

10. There is no evidence indicating that children born via IVF face a higher risk of developmental anomalies than those conceived naturally.

Gamete intrafallopian transfer (GIFT)

This technique is a variation of IVF and can be used when the Fallopian tubes are not blocked. It is primarily employed when the cause of infertility is unexplained or when cervical mucus has a detrimental effect on the partner's sperm, such as producing antibodies against them. The sperm and oocytes are introduced into the Fallopian tubes separately, meaning fertilization occurs naturally within the woman's body rather than outside it, as in IVF. The Introduction of Gametes is performed via laparoscopy or a newer transcervical method. Early embryos travel down the Fallopian tubes into the uterus, where they may implant. The success rate is around 21%, with higher chances of successful implantation compared to conventional IVF.

Zygote intrafallopian transfer (ZIFT)

This method is also used when the causes of infertility are unknown. However, unlike GIFT, zygotes rather than gametes are transferred into the tubes. The advantage of ZIFT is that fertilization is confirmed beforehand, whereas with GIFT this can only be verified once pregnancy is established. Compared to IVF, its advantage lies in the fact that early embryos reach the uterus naturally via the Fallopian tubes. The success rates for ZIFT are higher than those for either IVF or GIFT.

Donor insemination (DI)

If a man is infertile or has a very low sperm count, couples often choose donor insemination rather than adoption. This approach may also be used when the man is fertile but There is a risk of transmitting a genetic disorder to the child. The procedure is straightforward but requires thorough prior counselling.

Potential donors undergo comprehensive screening to assess their general health, fertility, family medical history, and to ensure their blood is free of antibodies to HIV, hepatitis B, and certain other infections that could be transmitted via semen. A donor is also chosen to match the prospective father in terms of race, height, Hair and eye color, build, and blood group. The Human Fertilisation and Embryology Act, which came into effect in 1991, requires that all records regarding donors and recipients be registered with a specialized statutory authority. Finally, legislation dictates that any person reaching the age of 18 has the right to access information regarding whether they were conceived via artificial insemination. However, the donor legally remains anonymous.

To maximize the chances of success, the woman undergoing the procedure is asked to track her basal body temperature to determine when ovulation will occur. She should also take clomiphene, which stimulates ovulation and makes its timing more predictable. On the appropriate day, thawed semen is carefully introduced into the cervical opening using a small plastic catheter. The success rate is very high, with the majority of women achieving pregnancy within 6 months.

Ethical issues

1. The primary issue concerns whether a child should know the identity of their biological father. The genetic father (donor) is not recognized as the legal father due to changes in legislation introduced in the late 1980s. Evidence suggests that children who have been told about their origins by their parents wish to learn more about their genetic fathers while maintaining warm relationships with their rearing parents. If the child is not told the truth, there is always a risk they will discover it at an inopportune time. The father may experience persistent anxiety that the child will find out, which can negatively affect their relationship.

2. If parents decide to inform the child, they must then determine the best time to do so and consider whether to disclose the information to extended family and friends. Professionals generally advise that it is better to tell the child sooner rather than later, ideally before adolescence.

3. It might be assumed that because the legal father is not the genetic father, he might struggle to maintain lifelong commitment to the child. However, there is no evidence that children conceived via donor sperm are loved any less. This is hardly surprising, considering the profound desire to have children required to go through all the necessary Procedures and counselling.

4. Should a child have legitimate access to information regarding their genetic father, and will this deter sperm donors from coming forward?

5. There is a possibility—albeit very small—that genetically related individuals born from donor insemination could inadvertently meet, form a relationship, and have children. Therefore, the number of successful live births resulting from any single donor's sperm must be restricted by law.

6. There is some debate over whether donor insemination should be available to unmarried couples, single women, and lesbians. In cases where a stable home environment is present, some clinics will consider such Applications. This is arguably preferable to individuals sourcing their own donors from family members, friends, or acquaintances, which frequently happens when they are denied access to donor insemination.

7. Some men and women view donor insemination as a form of adultery, perhaps for religious reasons, and are therefore fundamentally opposed to the procedure.

Artificial insemination by husband or partner (AIH)

This method is used in cases of certain forms of impotence and premature ejaculation, as well as when a man is about to undergo surgery (such as for testicular Cancer) or is living away from his family for extended periods. Some men leave written consent for their widows to use their stored semen posthumously—for instance, men serving in active military duty or suffering from a terminal illness. Using this method when sperm count is low is rarely effective, despite techniques available to concentrate semen samples. In such cases, IVF is a more suitable option.

Use of donor eggs

If a woman is unable to produce her own oocytes, the only viable solution is to use donor eggs. In this process, oocytes are retrieved using protocols developed for IVF, fertilized with the partner's sperm, cultured into early embryos, and transferred into the future mother's Fallopian tubes. Egg retrieval is significantly more demanding than sperm collection, and oocytes are notoriously difficult to cryopreserve. This complicates HIV screening. Nevertheless, surplus eggs from routine IVF or GIFT procedures can be utilized in this way.

Ethical issues are similar to those associated with donor insemination (see above).

Surrogacy

This approach may be used when a woman is unable to carry a pregnancy, for example, due to the absence of a uterus. In such arrangements, a contract is made with another woman who carries the pregnancy to term. She may undergo artificial insemination using the sperm of the intended father; alternatively, eggs can be harvested from the intended mother. An IVF or GIFT procedure is then performed to place the early embryo into the surrogate's uterus. It is also possible to use the surrogate's own egg, in which case direct insemination with the future father's sperm is sometimes used.

Ethical issues

1. In the United Kingdom, commercial surrogacy arrangements are currently illegal. This restriction is enforced to prevent the exploitation of infertile women.

2. Perhaps the most serious problem that may arise is the surrogate mother's refusal to surrender the newborn child to the intended parents. She may consider the baby her own. It is difficult to predict how a surrogate mother will behave when the time comes to give up the child.

3. Should the child be told about their origins? (We have already discussed this question in the context of donor insemination.)

4. If the surrogate mother falls ill or even dies As a result of the pregnancy, what would the legal consequences be? Can the people who hired her be sued? And if it becomes known that the child will be born with a disability, who should decide the question of abortion?

5. If the child is born with a disability, especially if the defect turns out to be genetic, the intended mother may refuse to accept the baby.

Subzonal insemination (SUZI), or microinsemination

SUZI is a recently developed technique in which several spermatozoa are placed near the oocyte using a very fine micropipette under microscopic observation. The sperm are deposited beneath the zona pellucida, hence the name "subzonal." Oocytes are retrieved in the same manner as for IVF. This method is not yet fully developed and remains of limited availability, but it appears highly promising.