Conception is a celebration in life for most of the people and the delayed conception or subfertility can have a stressful impact in your life. The reason for subfertility is different for different people. Both partners are expected to visit the fertility specialist at the first time. In the initial visit a detailed medical history and previous health reports will be reviewed. Blood tests, ultrasound scan and semen analysis will be done to understand the issues better and pave a way ahead for the treatment.

The most advanced and the most successful treatment for infertility is IVF (IN VITRO FERTILISATION and ICSI (INTRA CYTOPLASMIC SPERM INJECTION). Renai centre for Fertility and Reproductive health follow the following steps while performing an IVF cycle.

• Selection of Patients
• Pre-cycle Evaluation and counselling
• Ovulation Induction and Monitoring
• Egg Retrieval
• Sperm Processing
• In-Vitro Fertilization
• Embryo Transfer
• Post Transfer Management
• Cryo Preservation

Patients Selection

A complete evaluation of fertility factors (egg, sperm and uterine cavity) is important prior to considering IVF-ET technique. Tubal Disease – Patients with tubal blockage or severe pelvic adhesions, or those who have not conceived after tubal surgery are likely to respond to IVF-ET technique.

Patients with infertility due to Moderate to Severe Male Factor – The inadequate sperm count or motility issues can be handled effectively in the laboratory by various techniques, enabling the concentration of a large number of motile sperm around eggs through the IVF-ET technique. This is for couples whose infertility is due to poor semen quality. Couple with very low sperm count ICSI is advised

Patients with Endometriosis – This condition often results in pelvic anatomy distortion and adhesion. IVF-ET technique procedure allows the egg and sperm to meet and fertilize in an environment free of endometriomas and be transferred directly into the uterus.

Patients with unexplained infertility who have not responded to other types of therapy, IVF-ET is an effective therapy as it catalyzes the ability of the sperm to fertilize eggs. In rare instances unexplained infertility may be due to defects in gamete function.

Women with PCOS who are unable to conceive with Ovulation Induction or controlled ovarian hyperstimulation and IUI or those who need apreimplanation genetic evaluation for their offspring for various reasons ICSI is the option available.

Pre-cycle Evaluation

The success of the IVF-ET depends mainly on the ability of eggs, sperm and uterine cavity to respond to the treatment.

Various factors play a role in the pre-cycle evaluation.

• The woman’s ability to respond to fertility drugs has to be evaluated. Measurements of FSH (Follicle stimulating hormone that regulates the development, growth, pubertal maturation and reproductive processes of the body) and estradiol (female hormone) on second or third day of the menstrual cycle help us estimate a women’s ability to produce extra eggs in response to fertility drugs. In general women with high FSH levels and/or early high estradiol are more resistant to ovarian stimulation.
• The next step is the evaluation of the uterine environment. A regular trans vaginal scan with injecting saline to see the inside of the uterus is enough in most of the patients. But an office hysteroscopy is advised for those with suspicion of any intrauterine pathology or multiple failed cycles. Measuring the length of the uterus is also recommended as it helps the Doctor to understand the challenges of embryo transfer if any.
• Cervical cultures are a must before commencing treatment. Organisms such as urea plasma have been associated with poor reproductive outcome and poor embryonic growth in the laboratory.
• The uterine lining is evaluated prior to ovulation using a sonogram. Certain patterns of uterine lining development, especially when the lining is thin, are associated with poor pregnancy rates.
• Analysing the male factor with advanced semen analysis and semen culture is performed.
• Couples undergoing IVF-ET are screened for syphilis, hepatitis, HIV and HCV.
• Patients who are suffering from or have undergone any major medical, surgical or psychological problems need to consult their treating doctor before starting the programme and have to optimize their diseases and drugs taken prior to IVF cycle.
• Lifestyle modification which includes maintaining a healthy weight with balance diet and exercise, quitting active smoking and avoiding passive smoking, have a tight control in alcohol consumption are also advised.
• Patients are advised to take antioxidant supplements and other medications to regularize the endocrine imbalance if any (like thyroid supplementation).

Couples contemplating IVF-ET are advised to meet the counsellor who is familiar with emotional impact of infertility and treatment for the same. He/she can help them deal with the emotional turmoil. Couples are advised for suitable destressing methods like YOGA/MEDITATION/EXERCISE/MUSIC THERAPY.

Patients are also counselled for the approximate expense for the process and the payment schedules.

Ovulation Induction and Monitoring

IVF-ET success rates depend upon the numbers of eggs, fertilized eggs and good quality embryos available for transfer. Additionally, the egg retrieval must be carefully timed so as to retrieve mature eggs. To accomplish these goals, ovulation induction medications and careful monitoring are required. In most cases, the antagonist protocol or the long protocol (ovarian stimulation regimen) is followed. In antagonist protocol, an additional injection is started once the biggest follicle reaches 14 mm or estradiol reaches a particular level. In agonist protocol, patient (lady) is intramuscularly injected with decapeptyl depot 3.75mg (triptorelin 3.75mg) in their luteal phase (second half of the cycle – post ovulation period). The injection is usually given a week before (21st day of menses) of the upcoming treatment cycle day may vary to suit the cycle length of the patient. Sometimes progesterone may be prescribed to prevent premature ovulation.

After menses occurs, prior to starting the ovarian stimulation, we select a day for Down Check (a final check-up to ensure everything is in order as per requirement) in agonist protocol. In antagonist protocol injection is started at the second day of the periods. A scan is done to make sure there are no ovarian cysts, blood estradiol and progesterone levels are measured. When triptorelin is used, the ovaries remain quiescent until stimulation drugs are started. We arbitrarily call the first day of Gonadotropin administration cycle-Day1. IN order to monitor a patient’s response to these drugs. Sonograms and serum estradiol level checks are performed on Day4/5, Day7/8 and Day9/10. These help us to determine when the eggs are ready for collection.

Once the follicles (containing the eggs) are ready, the patient stops taking triptorelin or antagonist and Gonadotropins. About 36 hours prior to the anticipated egg retrieval, the patients takes an injection of Human Chronic Gonadotropin (Hcg) or agonist injection or both as decided by the doctor. This hormone replaces the women’s normal LH surge, and is necessary for a final maturation of the eggs so that they can be fertilized. After 12 hours of the final injection we do hormonal assessment (LH/ HCG) to assess the efficiency of the injection given.

Egg Retrieval

In almost all cases, egg retrieval is accomplished non-surgically using a vaginal ultrasound probe to guide a needle into the ovaries. The procedure is done under general anaesthesia (a lightest form of GA called TIVA) or with just simple intravenous sedation. An anaesthesiologist administers the sedation to maximise your comfort and safety. As a result, the experience is not painful and recovery is rapid. Procedure last for 15-30 mts.

Sperm Processing

Freshly ejaculated sperm must undergo biochemical and structural change called capacitation before they can fertilize an egg. In IVF-E.T sperm are capacitated in the laboratory and the motile and healthy sperms are isolated prior to inseminating the eggs

In-Vitro Fertilization/ICSI

In-Vitro Fertilization literally means ‘fertilization of glass’. Follicular fluid removed from the ovaries is examined in our lab for presence of eggs. These are isolated and placed in cultures media where they are allowed to further mature. A few hours later, portions of the processed sperms are placed around each egg. In a laboratory only about 50 to 100 thousand sperms are needed for each egg. This is why men with low sperm counts can often fertilize eggs in the lab.

The eggs and sperms are left to incubate together in a carefully controlled environment. Approximately 18 to 24 hours following insemination, the eggs are inspected under the microscope to determine how many have been successfully fertilized. These embryos will be kept in the laboratory as they continue to grow and develop until the moment of transfer.

For patients with severe male factor infertility, the best possible sperm is selected and manually injected into the egg with help of advanced instruments .

Embryo Transfer

The embryos are transferred via thin plastic tube through the cervix into the uterine cavity. They are then deposited in the upper part of the uterus and the catheter is withdrawn. This is generally a painless procedure and the patient is observed for 2 hours, after that she can go home. As the implantation will occur in the following few days, the patients are instructed to rest at home or do light work only during this time after the transfer. Light activities that do not cause stress are allowed and a good sleep at night is a must.

We usually transfer the embryos into the women’s uterus three days after the egg retrieval. At this stage, the embryos have cleaved and contain 8 cells each. We usually transfer 2 to 3 embryos depending on the quality (grading) of the embryos.

Post Transfer Management

During the follow-up phase, the women receives daily vaginal suppository of progesterone/+ oral progesterone with the goal of enhancing implantation. 14 days after the embryo transfer, blood and urine pregnancy tests are performed. Rising blood levels of pregnancy, HCG, indicate that implantation has occurred. Confirmation of a clinical pregnancy is made by ultrasound about 2 weeks later.

Cryo Preservation and cryotrasfer

Freezing extra embryos gives couples an additional opportunity to conceive without going through stimulation cycle and egg retrieval. After a menstrual cycle after egg pickup , patient is started on estradiol tablets to prepare the uterine lining. Prior to decision for thawing the embryos, an ultrasound assessment of the uterine lining is performed to make sure an adequate uterine environment is present and progesterone tablets are started. About more than 95% of frozen embryos survive the warming process.

Dr. Jisha Varghese

Sr. Specialist – Reproductive Medicine

Renai centre for Fertility & Reproductive Health