Assisted Reproductive Technology

• Assisted Reproductive Technology (ART) refers to a range of medical procedures used to help individuals and couples conceive a child when they face difficulties with natural conception. ART is designed to address various infertility issues and involves manipulating eggs, sperm, or embryos outside the body to achieve pregnancy.
• Modern treatment options to increase the chances of conception are now relatively simple, effective, and affordable, with promising success rates. These medical procedures aim to enhance egg and sperm production or facilitate their meeting, thereby increasing the chances of pregnancy. Collectively known as assisted reproductive technologies (ART), these procedures include methods such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

1.0Types of Assisted Reproductive Technology 

1. In Vitro Fertilization (IVF) 

• In vitro fertilization (IVF), meaning "fertilization in glass," now involves placing an egg and sperm together in a plastic dish rather than a test tube. 
• IVF is an assisted reproductive technique where fertilization occurs outside the body to create an embryo, which is then transferred to the uterus with the goal of implantation and pregnancy.

2. Intracytoplasmic Sperm Injection (ICSI)

• Intracytoplasmic Sperm Injection (ICSI) is a specialized form of in vitro fertilization (IVF) designed to address male infertility issues. 
• ICSI involves the direct injection of a single sperm into an egg to facilitate fertilization. 
• ICSI is often used when there are significant issues with sperm quantity, quality, or motility.
• IVF and ICSI are the most commonly used assisted reproductive technologies for achieving successful fertilization. 
• ICSI is typically employed when sperm have difficulty penetrating the egg's outer layer on their own. Once fertilization is achieved, the resulting embryo is transferred to the uterus, similar to the process in IVF.

3. Gamete Intrafallopian Transfer (GIFT)

• It is similar to IVF. In GIFT, the gametes (egg and sperm) are placed into the woman's fallopian tubes rather than her uterus, allowing fertilization within the body of the female.
• This procedure requires laparoscopy, a surgical method, to transfer the gametes to the fallopian tubes. GIFT is only suitable for women with normal fallopian tubes. 
• However, a limitation of GIFT is that fertilization cannot be directly confirmed, unlike with IVF.

4. Zygote intrafallopian transfer (ZIFT) 

• Zygote Intrafallopian Transfer (ZIFT) involves fertilizing eggs in a laboratory setting and then placing the resulting zygote (the fertilized egg) directly into the fallopian tube, rather than the uterus. This technique combines in vitro fertilization with the natural process of embryo implantation within the fallopian tubes. 
• ZIFT can be a suitable option for couples experiencing specific fertility issues, particularly when other assisted reproductive technologies (ART) have not achieved the desired results. 

5. Donor Sperm, Eggs, and Embryos

• Couples may opt for donor eggs or sperm if they encounter problems of their own or if they carry a genetic condition that might be transmitted to their child. 
• Donors can be known or anonymous, with donor sperm typically sourced from sperm banks. Both sperm and egg donors undergo rigorous medical and genetic screening and testing for infectious diseases.
• Donor sperm is frozen and held in quarantine for six months. After this period, the donor is retested for infectious diseases, including HIV. 
• The sperm is only approved for use if all tests are negative. Donor sperm can be utilized for both insemination and ART cycles, and using frozen sperm in IVF.
• Donor eggs are an option for women with a uterus who cannot conceive with their eggs. Egg donors undergo similar medical and genetic screening as sperm donors. 
• Egg donation involves more risk and inconvenience than sperm donation. Egg donation is a more complex process compared to sperm donation and is part of an IVF procedure. 
• The egg donor undergoes ovarian stimulation and egg retrieval, while the recipient receives hormonal treatments to prepare her uterus for embryo implantation. 
• Once retrieved, the donor’s eggs are fertilized with sperm from the recipient’s partner and then transferred into the recipient’s uterus. 
• Although the recipient does not have a genetic connection to the child, she becomes a biological parent by carrying the pregnancy and giving birth.

6. Assisted Hatching (AH)

• Assisted hatching (AH) is a micromanipulation procedure where a hole is created in the zona pellucida, the protective outer layer of the embryo, just before embryo transfer. This technique is intended to aid the embryo in hatching and uterine implantation. 
• AH has not been definitively shown to improve live birth rates overall, it may be considered for older women or couples who have experienced unsuccessful IVF attempts. For other groups of IVF patients, there is no clear evidence that AH enhances pregnancy or live birth rates.

7. Preimplantation genetic diagnosis (PGD)

• Preimplantation Genetic Diagnosis (PGD) is used at certain centres to screen for inherited diseases. During PGD, one or two cells are taken from a developing embryo and tested for specific genetic disorders. 
• Embryos that do not carry the gene associated with the disease are then selected for transfer to the uterus.

8. Surrogacy 

• A pregnancy can be carried by either an egg donor (traditional surrogate) or another woman with no genetic connection to the baby (gestational carrier). 
• If a traditional surrogate carries the pregnancy, conception may occur through insemination or ART. In this case, the surrogate is biologically related to the child. 
• In contrast, with a gestational carrier, the eggs are retrieved from the infertile woman, fertilized with her partner's sperm, and then transferred into the gestational carrier's uterus. 
• It is recommended that all parties involved in surrogacy or using a gestational carrier receive psychological and legal counseling before proceeding with the process.

2.0Preparation for ART

• Starting IVF can be preparing for approximately two months of medications, various procedures, and testing is important. 
• While modern fertility treatments generally have high success rates, multiple treatment cycles may be needed. The IVF process, up to the embryo transfer stage, typically takes about six to eight weeks and involves the following six stages:

Stage 1:

Ovarian Stimulation

• At the start of the menstrual cycle, the hypothalamus releases gonadotropin-releasing hormone (GnRH), which prompts the pituitary gland to secrete follicle-stimulating hormone (FSH). 
• FSH then stimulates the development of ovarian follicles, leading to the maturation of an egg. When the egg reaches maturity, the pituitary gland produces luteinizing hormone (LH), which triggers ovulation. 
• To increase the chances of conception, medications are given to stimulate the ovaries and prevent the early release of eggs. The aim is to produce several mature eggs, typically between five and ten, for fertilization.

Taking Fertility Medications:

• Gonadotropins: These medications, including synthetic FSH and sometimes a mix of FSH and LH, promote follicular development and are administered via self-injection.
• Human Chorionic Gonadotropin (hCG) is administered shortly before ovulation to trigger the final maturation and release of eggs.
• Luteinizing Hormone (LH): Supplemented for women with low natural LH levels to support follicle development.
• GnRH Agonists: These medications temporarily suppress natural hormone production to control premature ovulation and manage conditions like endometriosis. They include nafarelin acetate (nasal spray) and leuprorelin acetate (injection).
• GnRH Antagonists: Medications like cetrorelix acetate and ganirelix acetate are used to lower FSH and LH levels without causing an initial surge, reducing the risk of premature egg release.

Stage 2:

Egg Retrieval 

• Egg retrieval, or "egg pick-up," occurs just before expected ovulation, typically 36 to 48 hours after administering ovulation-inducing drugs. 
• Performed under mild sedation or anesthesia, this procedure uses an ultrasound-guided needle to aspirate eggs from mature follicles. 
• Sometimes, laparoscopy is used if the ovaries are difficult to access.

Stage 3:

Fertilization 

• Just before egg retrieval, a semen sample is collected from the male partner. 
• The sperm is then processed to select the most viable ones. In IVF, the sperm and eggs are combined in an incubator to facilitate fertilization. In ICSI, a single sperm is directly injected into an egg. 
• After 20 to 24 hours, the eggs are examined to confirm fertilization, and the resulting embryos are either transferred to the uterus or frozen for later use.

Stage 4:

Embryo Development 

•  Embryo Development following fertilization, embryos are cultured in the lab. 
• The doctor monitors their development and grades them based on quality. 
• Embryos are typically transferred between day two (2–4 cell stage) and day five (blastocyst stage), with blastocyst transfers preferred by some specialists due to improved selection of viable embryos.

Stage 5:

Embryo Transfer 

• Embryo transfer is a simple procedure, akin to a pap smear, and is typically done without anesthesia. 
• During the procedure, the embryo(s) are placed in a catheter and inserted into the uterus. 
• The number of embryos transferred is determined based on various factors, and any additional high-quality embryos may be frozen for future use. 
• It's important to note that transferring more embryos increases the risk of multiple pregnancies.

Stage 6:

Luteal Phase Support 

• In the two weeks following embryo transfer until the pregnancy test, it is advisable to rest for a few days before resuming usual activities. 
• Due to the previous treatments, the corpus luteum does not produce enough hormones for proper implantation. 
• To support the uterine lining, it will be prescribed progesterone, either as a vaginal gel or pessaries.
  

Success Rates 

Success rates are significantly affected by several factors, including:

• Age of the woman
• Underlying cause of infertility
• Response to medications and treatment
• Quality of sperm
• Number of embryos transferred
• Use of cryopreserved (frozen) embryos

3.0Infertility and Causes

It is the inability to conceive a child after a year of regular, unprotected intercourse for most couples or six months for women over 35. It can be caused by a variety of factors which includes:

• Ovulation Disorders : Conditions like polycystic ovary syndrome (PCOS) or hypothyroidism can disrupt the regular release of eggs.
• Fallopian Tube Blockage: Blocked or damaged fallopian tubes, often due to pelvic inflammatory disease (PID) or endometriosis, can prevent the egg and sperm from meeting.
• Endometriosis: Tissue similar to the uterine lining grows outside the uterus, affecting fertility by causing scarring and inflammation.
• Uterine Abnormalities: Structural issues with the uterus, such as fibroids or polyps, can interfere with implantation or pregnancy maintenance.
• Age: Fertility naturally declines with age, especially after 35.
• Hormonal Imbalances: Disorders affecting the balance of reproductive hormones can impact ovulation and fertility.
• Sperm Disorders: Low sperm count, poor sperm motility (movement), or abnormal sperm morphology (shape) can affect fertility.
• Blockages: Blockages in the reproductive tract can prevent sperm from being ejaculated.
• Genetic Disorders: Conditions like Klinefelter syndrome or Y-chromosome microdeletions can affect sperm production.
• Environmental and Lifestyle Factors