In the treatment of depression, today it is customary to use multiple therapeutic approaches in an integrated manner. Generally, we talk about drug therapy and psychotherapy. 

Transcranial Magnetic Stimulation aims to remodulate neuronal activity through the magnetic impulses emitted by a device and can be used both as an integration to traditional therapies, drugs and psychotherapy, to improve the effects of traditional treatments, and as an alternative to medical therapy. In particular, it can be indicated, together with psychotherapy, for those patients who have contraindications to taking drugs due to other pathologies (heart disease, liver disease, nephropathy) or in patients who refuse drug therapy due to experienced side effects or simple personal aversion. A very recent study from 2021, published by Publimed confirms the effectiveness of TMS in regressing the symptoms of drug-resistant depression.

The comprehensive TMS treatment program begins with a pre-TMS outpatient consultation evaluation, where the specialists assess your suitability for the treatment and provide answers to any queries you may have. In your initial treatment session, they conduct a brain mapping procedure to determine your unique TMS “dose”, ensuring a tailored approach to your therapy. Throughout your therapy journey, a trained TMS technician will closely monitor your daily progress and administer the TMS therapy. The TMS therapy may be optimized with other services aiming to restore your wellbeing, such as rehabilitation, cognitive exercises, consultations with psychologists and/or neurologists.

Throughout a TMS treatment session, you are comfortably seated in a reclined chair. You remain completely conscious and attentive, with the option to engage in conversation, listen to music, watch videos, or simply relax using earplugs.

An average treatment session typically spans from 20 to 30 minutes, during which you will experience a sequence of gentle taps on your head beneath the TMS coil. It’s not uncommon for certain patients to encounter slight discomfort on their scalp beneath the coil or occasionally experience a lingering headache after the initial few sessions. These sensations are ordinary, can be addressed by modifying the stimulation parameters, and usually dissipate within the initial week of daily sessions.

Similar to medications, the response time to TMS therapy can differ among patients. For optimal results in treating depression with TMS, it is advisable to undergo TMS sessions on weekdays consistently, typically spanning four to six weeks. It’s worth noting that, frequently, there may not be any noticeable shift in mood during the initial weeks of treatment. Clinical trials have shown that the majority of patients observed substantial benefits as early as the conclusion of the second week of TMS treatments, while a minority of needed more than 30 sessions before experiencing relief from depressive symptoms.

A study published in 2018 in The Lancet, a prestigious international scientific journal, reports that 47% of patients treated with TMS for major depression responded to therapy and 27% achieved remission of symptoms. Further studies show that TMS is a promising technology to treat neurological pathologies such as Alzheimer’s and Parkinson’s disease on which it seems to have efficacy in the remission of motor and cognitive symptoms.

In general, the data confirm the efficacy of transcranial magnetic stimulation in neurophysiological pathologies and its safety as a minimally invasive technique with low risk for the patient.

TMS offers a distinct advantage over other depression treatments by precisely honing in on the intended brain region or “target.” This precision allows clinicians to focus solely on specific areas of the brain while leaving others unaffected. TMS does not result in memory issues or cognitive impairments, nor does it alter a person’s personality. When patients find relief from their depression symptoms through TMS, they often experience improved cognitive abilities and overall functioning.

In comparison to other depression treatments, TMS is associated with minimal side effects. Research indicates that approximately one out of every five individuals may experience a mild to moderate headache or tenderness in the scalp following TMS treatment. These discomforts, however, typically resolve within the initial week and can be effectively managed.

The number of IVF cycles a person might need depends on several factors, including age, fertility issues, and overall health. Here’s an overview:

General Estimate

• On average, 1 to 3 IVF cycles are needed for a successful pregnancy.
• Some individuals may conceive in the first cycle, while others may require more.

Factors Influencing the Number of Cycles

1. Age:

   • Women under 35 often have higher success rates, requiring fewer cycles.
   • Women over 40 may need more cycles, as egg quality and quantity decline with age.

2. Fertility Issues:

   • Conditions like severe male factor infertility, poor ovarian reserve, or endometriosis may require additional cycles.

3. Embryo Quality:

   • Higher-quality embryos increase the likelihood of success in fewer cycles.

4. Lifestyle and Health:

   • Factors like weight, smoking, and overall health can influence outcomes.

5. Type of IVF Protocol:

   • Some may benefit from tailored protocols, such as natural cycle IVF, donor eggs, or genetic testing, which might reduce the need for multiple cycles.

Cumulative Success Rates

• The cumulative success rate increases with additional cycles:
  • 1st cycle: ~30-40% success (depending on age).
  • 2nd cycle: ~55-60% cumulative success.
  • 3rd cycle: ~70-80% cumulative success.

Embryo selection is a critical step in IVF, as it increases the chances of implantation and a successful pregnancy. Clinics use a combination of morphological assessment, time-lapse imaging, and genetic testing to choose the healthiest embryos.

1. Morphological (Visual) Assessment

Embryologists evaluate embryos under a microscope based on shape, symmetry, and cell division rate. The grading system depends on whether the embryo is at the cleavage stage (Day 3) or the blastocyst stage (Day 5-6).

Cleavage Stage (Day 3) Grading Criteria:

• Number of cells: Ideal embryos have 6-8 cells on Day 3.
• Cell symmetry: Evenly sized cells are preferred.
• Fragmentation: Less than 10% cell fragmentation is ideal.

Blastocyst Stage (Day 5-6) Grading Criteria:

• Expansion: A well-expanded blastocyst is preferred.
• Inner Cell Mass (ICM): This develops into the fetus. A strong ICM (graded A or B) is ideal.
• Trophectoderm (TE): These cells become the placenta. A well-defined TE (graded A or B) is preferred.

Example grading system: 4AA, 5AB, 3BB, where:

• First number: Expansion (1-6, with 5-6 being best).
• First letter: Inner cell mass quality (A = best, C = lowest).
• Second letter: Trophectoderm quality (A = best, C = lowest).

2. Time-Lapse Imaging (EmbryoScope)

Advanced IVF labs use AI-based time-lapse monitoring to track embryo development continuously. This helps:

• Identify embryos with normal cell division patterns.
• Detect abnormalities that may not be visible in static observations.
• Reduce stress on embryos by avoiding frequent handling.

3. Preimplantation Genetic Testing (PGT)

Some clinics perform genetic screening to select embryos without chromosomal abnormalities. This is especially useful for:

• Women over 35 (higher risk of chromosomal issues).
• Couples with recurrent miscarriage.
• Carriers of inherited genetic diseases.

Types of PGT:

• PGT-A (Aneuploidy Testing): Checks for chromosomal abnormalities (e.g., Down syndrome).
• PGT-M (Monogenic Disease Testing): Screens for specific genetic disorders (e.g., cystic fibrosis, sickle cell anemia).
• PGT-SR (Structural Rearrangements): Detects chromosomal translocations.

Yes, IVF can lead to ovarian hyperstimulation syndrome (OHSS), although modern protocols have reduced its occurrence. OHSS is an exaggerated response to hormonal stimulation, causing the ovaries to become swollen and painful due to fluid leakage into the abdomen.

What Causes OHSS?

OHSS is triggered by excessive ovarian stimulation from gonadotropins (FSH and LH) used in IVF. The risk increases if the ovaries produce too many follicles and respond aggressively to hCG (human chorionic gonadotropin), which is used to trigger ovulation.

Who Is at Risk?

Women with:

• Polycystic ovary syndrome (PCOS) (higher ovarian sensitivity).
• High antral follicle count (AFC) or high AMH levels.
• Young age (<35 years).
• Previous history of OHSS.
• High estradiol (E2) levels before trigger (>3500 pg/mL).
• Use of hCG as a trigger instead of a GnRH agonist.

Symptoms of OHSS

Mild to Moderate OHSS (Common)

• Abdominal bloating and discomfort.
• Nausea and vomiting.
• Enlarged ovaries.
• Mild weight gain due to fluid retention.

Severe OHSS (Rare but Serious)

• Rapid weight gain (>2 kg in 24 hours).
• Severe abdominal pain and swelling.
• Difficulty breathing due to fluid in the lungs.
• Decreased urination (kidney issues).
• Blood clots (increased risk of thrombosis).

How to Reduce the Risk of OHSS

1. Adjusting Stimulation Protocols

   • Use lower doses of gonadotropins in high-risk patients.
   • Use antagonist protocols (instead of agonist protocols).

2. Alternative Ovulation Triggering

   • GnRH agonist (e.g., Lupron) instead of hCG as a trigger shot reduces OHSS risk.
   • Avoid fresh embryo transfer and do a “freeze-all” cycle to allow recovery.

3. Medication to Prevent OHSS

   • Cabergoline helps reduce fluid accumulation.
   • IV albumin can prevent severe fluid shifts.

4. Post-Retrieval Monitoring & Hydration

   • Drink plenty of fluids with electrolytes.
   • Avoid intense physical activity.
   • Frequent monitoring to detect early signs of OHSS.

Does OHSS Affect Pregnancy?

• Mild cases do not impact pregnancy outcomes.
• Severe OHSS may require hospitalization, delaying embryo transfer.
• If pregnancy occurs in an OHSS cycle, symptoms can worsen due to rising hCG levels.

In patients with Parkinson’s, transcranial magnetic stimulation is used to support traditional pharmacological therapy, and the maximum benefit is obtained when the patient also follows courses of physiotherapy or, better to say, neuromotor rehabilitation. In this case, in fact, the area of the brain that is stimulated through the magnetic waves is the motor cortex, which is one of the main areas of the brain responsible for movement control. TMS in combination with physiotherapy allows the patient to have improvements on the motor symptoms of the disease.

In patients with Alzheimer’s, TMS remodulates the plasticity of the precuneus, an area of the brain involved in memory functions. Recent scientific evidence has shown that this brain structure is one of the first to ‘suffer’ from Alzheimer’s disease and is already compromised in the prodromal stages of the disease. However, in typical forms of Alzheimer’s, the brain structures primarily involved in degenerative phenomena are those located in the medial temporal lobes. In fact, the early stages of the disease are dominated by memory disturbances. The neuromodulatory strategy using TMS consists in stimulating the precuneus, which, at least in part, suffers due to mechanisms of disconnection with the medial temporal structures. This neuromodulation has been shown to be effective in slowing the progressive accumulation of cognitive deficits, the aggravation of which leads individuals with initial Alzheimer’s disease to a state of dementia.

Timing is therefore very important in treatment: in fact, stimulation is more effective in early Alzheimer’s. This makes a precise diagnosis from the first symptoms and a careful evaluation by the neurologist essential to maximize the benefits of the treatment, which must be administered with anatomical accuracy on the basis of neuroimages obtained with Magnetic Resonance. The ultimate goal is to improve memory, slowing down the degenerative process of the brain cells (neurons) of the precuneus and the structures connected to it, which perform important cognitive functions.

Transcranial magnetic stimulation, TMS, together with cognitive behavioral therapy, CBT (Cognitive Behavioral Therapy), helps reduce the desire to smoke or to consume other psychostimulant substances, if used frequently.

The brain regulates emotions especially through the limbic system, composed of a series of nuclei and deep nerve fibers that connect, among others, with the orbito-frontal cerebral cortex, an area of the brain that plays a fundamental role in the emotional response and in the subsequent decision-making. The regulation function of this system, both for its activation and for its inhibition, is carried out by neurotransmitters, chemical substances naturally present in the nervous system, which have the ability to excite or inhibit the brain circuits responsible for the development of emotions and many other functions of the nervous system.

Nicotine, and psychostimulants in general, interfere with the action of various neurotransmitters. Simply put, these substances alter the messages that the brain processes in particular in the limbic system. The mechanisms through which these substances carry out this action are different but, in general, it can be said that they modify the quantity of some neurotransmitters present in our brain such as dopamine, a neurotransmitter useful for consolidating memory and a mediator of pleasant sensations, and glutamate, which favors the exchange of information between neurons and has a stimulating and natural activation function of the circuits of our nervous system.

Psychostimulant substances or an excess of psychoactive drugs introduced into the body from the outside, through the activation of the circuits of the limbic system, intensify the sensation of pleasure and sense of gratification. Hence a sensation of false well-being which, in the event of problematic and prolonged use, leads to addiction and a desire that is difficult to control, defined as craving, to take the psychostimulant substance to which the whole organism, and in particular the brain, is by now used to it.

TMS and cognitive-behavioral therapy, used in synergy, are effective for treating patients who make problematic use of nicotine or other psychostimulant substances. The aim of treatment is for the person to have the opportunity to choose to stop using nicotine or other psychoactive substances, without being dominated by craving. This is possible only by restoring decision control, which occurs above all in the orbito-frontal area of the brain, freeing this function from the conditioning of false emotions. The process, from the initial clinical assessment of the patient to the completion of the series of TMS treatment sessions, takes approximately one month. In some cases it is useful to continue with boosters with TMS sessions in the following months.

IVF failure can occur at different stages:

• Poor ovarian response: The ovaries may not produce enough eggs.
• Failed fertilization: Eggs and sperm may not combine successfully.
• Poor embryo quality: The embryos may not develop properly.
• Implantation failure: The embryo may not attach to the uterine lining.
• Early miscarriage: Even if implantation occurs, the pregnancy may not progress.

The doctor will review your cycle to determine potential reasons for failure. The next steps after IVF failure are:

• Medical evaluation: A fertility specialist may recommend additional tests, such as genetic screening, hormone testing, or uterine evaluation.
• Changes in protocol: Adjustments in medication, different stimulation protocols, or using donor eggs/sperm may be suggested.
• Lifestyle adjustments: Improving diet, reducing stress, and addressing any underlying health conditions can help.
• Considering other options: If multiple IVF attempts fail, options like donor embryos might be discussed.