What are the steps to initiate and proceed with In Vitro Fertilization (IVF) treatment?

How to Initiate and Proceed with In Vitro Fertilization (IVF) Treatment

IVF treatment requires ovarian stimulation for oocyte retrieval followed by fertilization and embryo transfer, with the entire process taking more than a week and yielding approximately 37% live delivery rate per initiated cycle. 1

Step 1: Initial Consultation and Treatment Planning

Counsel patients that IVF success rates are closely related to female age, with progressively lower success rates over 35 years. 1 Discuss that approximately 12.5% of deliveries involve twins if multiple embryos are transferred, and additional pregnancies may result from cryopreserved embryos. 1

Provide clear information about risks of multiple pregnancy if more than one embryo transfer is considered, including higher rates of pregnancy loss, ectopic pregnancy, pre-eclampsia, gestational diabetes, hemorrhage, Caesarean section, stillbirth, preterm birth, low birthweight, NICU admission, and neonatal death. 1 Patients should sign an additional consent form if more than one embryo will be transferred. 1

Discuss cost-related information at the treatment planning stage, including increased direct costs for obstetric and pediatric care of multiples, plus indirect costs from sick leave and loss of productivity. 1

Step 2: Ovarian Stimulation Protocol Selection

For patients with acceptable ovarian reserve, use routine ovarian stimulation protocols to obtain more embryos for genetic testing and transfer. 1 The GnRH antagonist protocol is recommended for high responders to prevent ovarian hyperstimulation syndrome. 1

For poor responders where oocyte collection fails after routine stimulation, consider alternative protocols including natural cycle retrieval, minimal ovarian stimulation, or luteal phase stimulation. 1 Counsel these patients about risks of low oocyte numbers, no transferable embryos, or cycle failure. 1

Administer hCG (5000-10,000 IU) after ovarian stimulation, with oocyte retrieval performed within 36-38 hours. 1

Common Stimulation Agents

• Clomiphene citrate occupies estrogen receptors, triggering GnRH release and subsequent FSH/LH rise for follicular development 2
• Human menopausal gonadotropin (hMG/menotropins) provides both FSH and LH for multiple follicular development 2
• Highly purified FSH can be administered subcutaneously with 90% purity 2
• Recombinant human FSH offers complete LH-free formulation with better batch consistency and greater purity 2

Step 3: Oocyte Retrieval and Fertilization

Use intracytoplasmic sperm injection (ICSI) for all IVF cycles to minimize interference from maternal granulosa cells and paternal spermatozoa in genetic testing accuracy. 1 This is particularly important for preimplantation genetic testing cycles. 1

Conscious sedation with midazolam, pethidine (meperidine), and fentanyl is nontoxic for oocyte recovery. 2 If full anesthesia is required, balanced anesthesia with nitrous oxide and an opioid is the most appropriate option. 2

Step 4: Embryo Culture and Selection

Culture embryos to blastocyst stage (Day 5 or 6 after ICSI) for optimal selection and transfer. 1 Blastocyst trophoblast cell biopsy is the main method if genetic testing is performed, as it has minimal effect on embryo development potential. 1

For blastocyst biopsy, operate away from the inner cell mass and biopsy five to eight trophoblast cells. 1

Step 5: Embryo Transfer Strategy

Transfer only a single embryo (eSET) in the following situations:

• Normal responders to ovarian stimulation 1
• Low or high ovarian responders 1
• Patients using donor oocytes 1
• Patients using donated embryos 1
• Gestational carriers 1

The decision to perform double embryo transfer (DET) instead of single embryo transfer should NOT be based on:

• Endometrial characteristics in fresh cycles 1
• Endometrial characteristics in frozen cycles 1
• Number of previous failed cycles 1

Step 6: Freeze-All Strategy and Timing

Apply a 'freeze-all' embryo strategy in fresh cycles when using GnRH antagonist protocols. 1 This allows for optimal endometrial preparation in a subsequent frozen embryo transfer cycle.

Use progesterone supplementation in the luteal phase, administered by intramuscular injection or vaginal suppository. 2

Step 7: Post-Transfer Management and Follow-Up

Prescribe one year's supply of any hormonal medications needed to reduce barriers to continued use. 1 Document patient understanding of use, benefits, and risks, plus create an individualized follow-up plan. 1

Counsel patients that bleeding irregularities are generally not harmful and may resolve with continued medication use. 1

Critical Pitfalls to Avoid

Never prescribe exogenous testosterone therapy to males interested in current or future fertility, as it provides negative feedback to the hypothalamus and pituitary, resulting in inhibition of spermatogenesis. 1 This is a common error that can cause azoospermia requiring months to years for recovery. 3

For males with hypogonadotropic hypogonadism requiring fertility treatment, use hCG injections (500-2500 IU, 2-3 times weekly) as first-line therapy to restore testosterone production and spermatogenesis, followed by FSH injections when indicated after testosterone normalization. 1

For males with elevated sperm DNA fragmentation, consider testicular sperm retrieval (TESA or TESE) as these procedures may offer viable sperm with lower DNA fragmentation, potentially improving assisted reproduction outcomes. 1

Special Populations

Provide high-quality care in an accommodating, nonjudgmental environment for all patients, including adolescents, those identifying as LGBTQ+, and patients with disabilities or limited English proficiency. 1

For obstructive azoospermia with confirmed ejaculatory duct obstruction, consider transurethral resection of ejaculatory ducts (TURED) and/or surgical sperm extraction to allow sperm to enter the ejaculate for use in IUI or ART. 1