In Vitro Fertilization

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Overview of In Vitro Fertilization (IVF) and Assisted Reproductive Technology (ART)

Assisted Reproductive Technology (ART) encompasses medical techniques involving the manipulation of oocytes outside the human body to achieve pregnancy. The most widely used form is in vitro fertilization (IVF), where fertilization occurs in a laboratory dish rather than within the female reproductive tract. The term "in vitro" translates to "in glass," reflecting the external environment where oocytes and sperm meet.

The first successful IVF birth was reported in July 1978 in England by Dr. Robert Edwards and Dr. Patrick Steptoe—a milestone that earned Dr. Edwards the Nobel Prize in Medicine in 2010. Since then, the field of reproductive endocrinology and infertility (REI) has expanded dramatically. IVF now accounts for approximately 1.6% of live births in the United States and 4.5% in Europe.

Initially developed to overcome tubal factor infertility, IVF is now used for various causes, including male factor infertility, endometriosis, unexplained infertility, and age-related decline in ovarian reserve. It also allows for the use of donor oocytes or embryos in women with diminished ovarian function and provides fertility preservation options for individuals undergoing gonadotoxic treatments.

Female Reproductive Anatomy and IVF Relevance

Understanding female pelvic anatomy is essential in IVF. The uterus, derived from the Müllerian ducts, comprises three layers: the serosa, myometrium, and endometrium. The endometrium, a hormonally responsive glandular tissue, plays a key role in embryo implantation and successful pregnancy. Anatomical or structural abnormalities can impair IVF success.

Defining and Diagnosing Infertility

Infertility is defined as the inability to conceive after 12 months of unprotected intercourse (6 months if the woman is ≥35 years). Roughly 10–15% of couples are affected. Initial evaluation includes:

  • Assessment of ovulatory function and ovarian reserve

  • Semen analysis

  • Imaging of the uterine cavity and tubal patency

  • Diagnostic laparoscopy for suspected endometriosis or tubal pathology

Common Indications for IVF

1. Tubal Disease

Approximately 25–35% of female infertility cases involve tuboperitoneal disease, often due to pelvic inflammatory disease (PID), with Chlamydia trachomatis being a common pathogen. IVF circumvents tubal damage by directly transferring embryos into the uterus.

2. Endometriosis

A chronic inflammatory condition marked by endometrial tissue outside the uterus. It impairs fertility via inflammation, adhesions, and altered folliculogenesis. IVF success rates are lower in advanced cases.

3. Male Factor Infertility

Responsible for 20–40% of infertility cases. IVF with intracytoplasmic sperm injection (ICSI) can overcome severe sperm abnormalities or obstructive azoospermia.

4. Diminished Ovarian Reserve and Donor Oocytes

Donor oocytes are used when a woman’s own oocytes are nonviable due to aging or primary ovarian insufficiency (POI).

5. Fertility Preservation

Women undergoing chemotherapy, radiation, or elective delay of childbearing may cryopreserve oocytes or embryos for future use.

Contraindications to IVF

There are no absolute contraindications to IVF itself, but pregnancy should be avoided in patients with high maternal risk, such as those with:

  • NYHA class III/IV heart failure

  • Eisenmenger syndrome

  • Severe pulmonary hypertension

  • Marfan syndrome with aortic involvement

In such cases, IVF may be performed with embryo transfer to a gestational carrier.

IVF Equipment and Personnel

Laboratory Equipment

  • Gas-controlled incubators, water baths, microscopes

  • Micromanipulation tools for ICSI

  • Cryopreservation systems

  • Laser for preimplantation genetic testing (PGT)

Personnel

  • REI-trained physician

  • Reproductive medicine-trained nurse

  • Ultrasonography-trained clinician

  • Certified embryologists and laboratory director

Patient Preparation

Evaluation includes:

  • Ovarian reserve testing: Day 3 FSH/E2, AMH, or antral follicle count

  • Semen analysis

  • Uterine imaging: HSG or saline sonogram

  • Infectious disease screening: HIV, Hepatitis B/C, Syphilis

IVF Procedure

1. Ovarian Stimulation

Protocols vary:

  • Long GnRH agonist

  • GnRH antagonist

  • Minimal stimulation (e.g., clomiphene, letrozole)

Monitoring involves serial ultrasounds and estradiol levels. hCG is administered to trigger final oocyte maturation when follicles reach ≥18 mm.

2. Oocyte Retrieval

Occurs 34–36 hours post-hCG injection via transvaginal ultrasound-guided aspiration under sedation.

3. Fertilization

  • Conventional insemination or ICSI

  • Sperm are processed and incubated with oocytes

  • ICSI is used for male factor infertility or previously failed fertilization

4. Embryo Transfer

Occurs on day 3 (cleavage stage) or day 5 (blastocyst stage). Blastocyst transfer offers higher success rates with fewer embryos transferred, reducing multiple gestations.

Guidelines suggest:

  • ≤2 blastocysts for women <37

  • ≤3 blastocysts for ages 38–40

  • ≤4–5 cleavage stage embryos for older age groups

5. Luteal Support

Progesterone supplementation begins post-retrieval or post-transfer to support endometrial receptivity.

Complications

  • Ovarian Hyperstimulation Syndrome (OHSS): Can range from mild discomfort to life-threatening complications (e.g., ascites, thromboembolism, renal failure). Severe OHSS affects ~0.2–1% of cycles.

  • Multiple Gestations: IVF contributes to increased twin and triplet rates, associated with higher risks of preterm birth and hypertensive disorders.

  • Singleton IVF Outcomes: Increased risks of gestational diabetes, low birth weight, cesarean delivery, and congenital anomalies have been observed compared to naturally conceived singletons.

Clinical Significance and Outcomes

Infertility affects 1 in 8 couples in the U.S. Over 5 million children globally have been conceived via IVF. According to the Society for Assisted Reproductive Technology (SART):

Live Birth Rates by Age (per intended retrieval):

  • <35 years: 47.6%

  • 35–37 years: 30.7%

  • 38–40 years: 21.7%

  • 41–42 years: 10.4%

  • 42 years: 3.1%

Singleton rates are high (>89%) across all age groups, with twin and triplet rates decreasing due to improved embryo transfer guidelines.

Interdisciplinary Collaboration and Patient Support

Successful IVF treatment requires coordination among physicians, nurses, ultrasonographers, and embryologists. Equally important is addressing the psychological burden of infertility. Lack of emotional support is a known factor contributing to treatment discontinuation and lower success rates. Patient-centered communication and psychological support are critical to optimizing care.

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