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Risks of IVF

Course /Risks of IVF

Summary

Course Objective: To provide a clear, step-by-step overview of the medical journey of In Vitro Fertilization (IVF) within the context of a surrogacy arrangement.

Course Content:

Introduction

The path to parenthood through surrogacy is a collaborative journey involving Intended Parents, a Gestational Carrier, and a dedicated medical team. The core medical procedure that makes this possible is In Vitro Fertilization (IVF). This course outlines the synchronized steps for all parties involved.

The Synchronized Phases of IVF for Surrogacy

  1. Phase 1: Ovarian Stimulation & Monitoring (For the Intended Mother or Egg Donor)
    • The cycle begins with the administration of hormonal injections (gonadotropins) to stimulate the ovaries to develop multiple follicles, each containing a potential egg.
    • This phase is closely monitored via transvaginal ultrasounds and blood tests to track follicle growth and hormone levels, allowing for precise medication adjustments.
    • The goal is to achieve optimal development for a successful egg retrieval.
  2. Phase 2: Egg Retrieval & Sperm Collection
    • Once follicles reach an appropriate size, a “trigger shot” (hCG or Lupron) is administered to finalize egg maturation.
    • Approximately 36 hours later, the egg retrieval is performed. This is a minor surgical procedure under sedation, where a needle is guided through the vaginal wall to aspirate fluid and eggs from each follicle.
    • On the same day, a sperm sample is provided by the Intended Father or sperm donor.
  3. Phase 3: Fertilization & Embryo Development (In the Lab)
    • In the embryology lab, the retrieved eggs are inseminated with sperm. This is often done via Intracytoplasmic Sperm Injection (ICSI), where a single sperm is injected directly into an egg to maximize fertilization chances.
    • The fertilized eggs (now embryos) are cultured in a specialized incubator for 5-7 days, allowing them to develop into blastocysts, the optimal stage for transfer or freezing.
  4. Phase 4: Embryo Transfer (To the Gestational Carrier)
    • This is a critical synchronization point. The Gestational Carrier’s uterine lining is prepared with estrogen and progesterone to be perfectly receptive for embryo implantation.
    • The embryo transfer is a simple, painless procedure where one or more selected embryos are transferred into the carrier’s uterus using a thin catheter.
    • Any remaining high-quality embryos are typically cryopreserved (vitrified) for future use.
  5. Phase 5: The Two-Week Wait & Pregnancy Test
    • Following the transfer, the Gestational Carrier continues progesterone support to sustain the uterine lining.
    • Approximately 9-12 days post-transfer, a blood test (beta hCG) is performed to confirm pregnancy.

Ovarian Hyperstimulation Syndrome (OHSS)

Course Objective: To educate patients on the causes, symptoms, and management of OHSS, a potential complication of ovarian stimulation.

Course Content:

What is OHSS?
Ovarian Hyperstimulation Syndrome (OHSS) is an exaggerated response to fertility medications, particularly the “trigger shot” used to induce final egg maturation. It causes the ovaries to become enlarged and fluid to leak into the abdomen.

Causes and Risk Factors
OHSS is primarily triggered by high levels of hCG (Human Chorionic Gonadotropin). Key risk factors include:

  • Polycystic Ovary Syndrome (PCOS)
  • High Anti-Müllerian Hormone (AMH) or Antral Follicle Count (AFC)
  • A large number of developing follicles
  • High estrogen levels during stimulation
  • Pregnancy, which produces endogenous hCG

Symptoms: From Mild to Severe

  • Mild to Moderate: Abdominal bloating, discomfort, nausea, and slight weight gain.
  • Moderate to Severe: Significant abdominal distension and pain, persistent nausea and vomiting, rapid weight gain (>2 lbs/1 kg in 24 hours), reduced urine output, and shortness of breath.

Prevention and Proactive Management
Modern IVF practices have significantly reduced the incidence of severe OHSS. Key strategies include:

  • Using an Agonist Trigger: Replacing hCG with a Lupron trigger in high-risk patients.
  • “Freeze-All” Strategy: Electively freezing all embryos and postponing transfer to a future, natural cycle. This eliminates the risk of pregnancy-induced OHSS.
  • Coasting: Withholding gonadotropin injections for a day or two before the trigger shot.
  • Cabergoline: A medication that can help reduce the risk of OHSS.

Treatment
Treatment is supportive and depends on severity. It ranges from oral hydration and monitoring for mild cases to hospitalization for intravenous fluids, pain management, and, in rare cases, paracentesis (draining of abdominal fluid) for severe cases.

Issues Associated With Twin or Triplet Pregnancies

Course Objective: To explain the significant medical risks associated with multiple gestation pregnancies, reinforcing the rationale for Single Embryo Transfer (SET).

Course Content:

The Shift in Practice
While twins were once a common outcome of IVF, reproductive medicine has moved decisively towards Single Embryo Transfer (SET) due to the profound risks that multiples pose to both the mother and the babies.

Risks to the Gestational Carrier

  • Pregnancy-Induced Hypertension & Preeclampsia: The risk is significantly higher in multiple pregnancies.
  • Gestational Diabetes: More common and often more difficult to manage.
  • Preterm Labor & Birth: The vast majority of twin and nearly all triplet pregnancies deliver prematurely (<37 weeks).
  • Placental Complications: Higher incidence of placenta previa and placental abruption.
  • Cesarean Delivery: The likelihood of requiring a C-section is greatly increased.

Risks to the Offspring

  • Prematurity: This is the single greatest risk. Premature babies are at risk for:
    • Low birth weight
    • Respiratory Distress Syndrome (RDS)
    • Intraventricular hemorrhage (bleeding in the brain)
    • Necrotizing enterocolitis (a serious intestinal condition)
    • Long-term neurodevelopmental delays
  • Intrauterine Growth Restriction (IUGR): One or both babies may not grow at an appropriate rate.
  • Congenital Anomalies: The risk of birth defects is slightly higher in multiples.
  • Twin-to-Twin Transfusion Syndrome (TTTS): A serious complication unique to identical twins sharing a placenta, where blood flow becomes unbalanced.

The Standard of Care: Elective Single Embryo Transfer (eSET)
With advances in embryo selection (e.g., PGT-A and blastocyst culture), the success rate for a Single Embryo Transfer is now very high. eSET is the recommended practice to ensure the healthiest possible outcome for the Gestational Carrier and the child.

Risk of Birth Defects To Offspring

Course Objective: To provide a balanced and evidence-based perspective on the slight increase in birth defect risk associated with ART.

Course Content:

Understanding the Baseline Risk
It is first essential to understand that in the general population, the risk of a major birth defect is approximately 2-3%. This is the baseline against which all ART outcomes are measured.

What Does the Research Show?
Large-scale studies and meta-analyses have concluded that there is a small but statistically significant increase in the risk of birth defects in children conceived through IVF and ICSI. The absolute increase is generally estimated to be about 1-1.5% above the baseline, bringing the total risk to approximately 3-4%.

Potential Contributing Factors
The exact cause is not fully understood, but theories include:

  • The Underlying Infertility: The condition that caused the infertility itself may be linked to a higher risk of genetic anomalies.
  • The ICSI Procedure: The slight increase is more pronounced with ICSI, possibly related to bypassing natural sperm selection or the genetic quality of the sperm used.
  • Epigenetic Changes: The laboratory environment may cause subtle alterations in gene expression, though this is an area of ongoing research.

Important Context and Reassurance

  • The vast majority of children conceived via IVF are born healthy.
  • Preimplantation Genetic Testing (PGT) can screen for specific chromosomal abnormalities (like Down syndrome) and some genetic disorders, potentially reducing the risk of certain conditions.
  • The absolute risk remains low, and for most couples, the benefit of achieving a pregnancy far outweighs this small increased risk.

Fetal Death and Other Complications

Course Objective: To discuss the difficult topic of pregnancy loss and other obstetric complications at different stages of pregnancy.

Course Content:

The Reality of Pregnancy Loss
Sadly, pregnancy loss can occur at any stage, and pregnancies achieved through ART are not immune to this risk. Understanding these risks is part of being prepared for the journey.

First Trimester: Miscarriage

  • The risk of miscarriage in IVF pregnancies is comparable to that in the general population and is strongly linked to maternal age.
  • The primary cause of early miscarriage is chromosomal abnormalities in the embryo.
  • The use of PGT-A can reduce, but not eliminate, the risk of miscarriage by selecting chromosomally normal (euploid) embryos for transfer.

Second and Third Trimester: Stillbirth
Stillbirth (fetal death after 20 weeks) is a devastating outcome. Some studies suggest a slightly higher rate in ART-conceived pregnancies, which may be related to:

  • The higher rate of multiple pregnancies (a known risk factor for stillbirth).
  • The underlying maternal health factors that contributed to infertility.
  • Placental complications.

Other Obstetric Complications
IVF pregnancies are often managed as “high-risk” due to associations with:

  • Placenta Previa: The placenta implants low in the uterus, covering the cervix. This is more common in IVF pregnancies.
  • Placental Abruption: The premature separation of the placenta from the uterine wall.
  • Preterm Premature Rupture of Membranes (PPROM): The water breaking before 37 weeks.
  • Cesarean Delivery: Higher rates are observed, often due to the “precious” nature of the pregnancy or associated complications.

A Few Words About Cancer

Course Objective: To address common patient concerns regarding a potential link between fertility drugs and cancer risk.

Course Content:

A Topic of Concern and Misinformation
The question of whether fertility drugs cause cancer is one of the most studied and debated topics in reproductive medicine. It is a natural concern, given that these medications influence hormone levels.

The State of the Evidence
After decades of large, robust studies, the overall consensus in the medical community is that there is no strong consistent evidence that the use of fertility drugs significantly increases a woman’s overall lifetime risk of cancer.

Important Nuances
While the overall risk does not appear to be elevated, research has focused on two specific cancer types due to their hormone-sensitive nature: breast and ovarian cancer. The following courses will address these in detail.

Key Takeaways:

  1. No Causal Link Established: Multiple large cohort studies have failed to prove a causative link between fertility medications and a general increase in cancer incidence.
  2. Confounding Factors: A major challenge in this research is “confounding.” Women who experience infertility (nulliparity, not having breastfed, etc.) may already have a different baseline risk for certain cancers compared to the fertile population.
  3. Ongoing Vigilance: The medical community continues to monitor this through long-term registries and studies.

Breast Cancer Risk

Course Objective: To specifically analyze the data on fertility medications and breast cancer risk.

Course Content:

The Theoretical Concern
Because some forms of breast cancer are estrogen-receptor-positive, and fertility drugs temporarily increase estrogen levels, a theoretical concern exists.

What Do the Studies Show?
The vast majority of large-scale, well-designed studies have found no significant association between the use of fertility drugs and an increased risk of breast cancer. Several studies have followed IVF patients for 20-30 years, providing substantial long-term data.

Key Research Findings:

  • A 2019 Danish study of over 58,000 women found no overall increase in breast cancer risk among those who received fertility treatments.
  • A 2020 study from the Netherlands, with a 24-year follow-up, concluded that IVF treatment was not associated with an increased risk of breast cancer.
  • Some studies have even suggested a possible “protective” effect, though this is not a confirmed finding.

Considerations

  • As with overall cancer risk, the underlying characteristics of infertile women (such as having a first child at a later age) can complicate the analysis.
  • The current body of evidence is overwhelmingly reassuring.

Ovarian Cancer Risk

Course Objective: To clarify the complex relationship between infertility, fertility drugs, and ovarian cancer risk.

Course Content:

Untangling a Complex Relationship
The relationship between ovarian cancer and fertility drugs is the most complex of these discussions, primarily because it is deeply intertwined with the underlying condition of infertility itself.

The Known Risk Factor: Infertility
It is well-established that women who have never been pregnant (nulliparity) have a higher baseline risk of ovarian cancer compared to women who have had children. Therefore, the population seeking IVF already enters with a potentially elevated risk profile due to their infertility.

The “Ovarian Stimulation” Question
Early studies caused alarm, but later, more rigorous research has provided crucial context:

  • No Overall Increase: Most large, modern studies have found that the use of fertility drugs does not significantly increase the overall risk of ovarian cancer when compared to other infertile women.
  • The Role of Endometriosis: Some studies indicate that the slight increase in risk observed in certain subgroups may be linked to specific causes of infertility, such as endometriosis, which is itself a known risk factor for certain types of ovarian tumors.
  • Borderline Tumors: Any potential slight increase in risk appears to be associated with low-malignant-potential (borderline) tumors, not with invasive ovarian cancer. Borderline tumors have an excellent prognosis.

The Protective Effect of Pregnancy
It is important to note that achieving a successful pregnancy via IVF may actually reduce a woman’s lifetime risk of ovarian cancer by bringing her risk profile closer to that of a parous (child-bearing) woman.

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