What is Infertility?
Infertility is defined as not being able to conceive even after trying for over a year of having unprotected intercourse. Nearly 15% of the couples fail to have children naturally, and the cause could be either in you or your partner, or a combination of reasons. Infertility also includes the cases where the female is unable to sustain pregnancy.
The advanced techniques of Assisted Reproduction have given hopes to several couples who have succeeded in completing their family.
Infertility can be attributed to various factors in males and females, but there is no single underlying reason for it.
Female infertility could be due to ovulatory and anatomical disorders. These could be either due to inability of the egg to reach uterus or inability of the ovaries to release egg. It could also be due to damaged fallopian tubes. Sometimes a fertilized egg fails to attach to the uterus lining; and at times, an attached embryo fails to survive. Female infertility could also be due to certain other conditions such as autoimmune disorders, diabetes, tumors, and cancers, and certain hormonal problems such as thyroid or hyperprolactinemia. In certain other cases, infections such as Chlamydia, tuberculosis, gonorrhea in the womb can also contribute to infertility in women.
Whereas, male infertility could be due to blockage of sperm production or decreased sperm count. Apart from these, there are other risk factors, which could contribute to infertility in many, if not all the cases. These risk factors could be lack of sufficient nutrition, excessive smoking, sexually transmitted infections, or exposure to certain chemicals such as pesticides, herbicide, lead metal etc.
What is the incidence of infertility worldwide?
According to the World Health Organization (WHO) data, nearly 8-10% of couples all over the world are affected by one or other kind of infertility, with numbers ranging between 50 and 80 million. However, the incidence of such a condition may vary from one region to another.
Is infertility exclusively a female problem?
No, infertility is not exclusively the problem with females. Nearly 30-40% of couples who cannot conceive due to infertility are due to the female partner, while an equal proportion, i.e. in 30-40% of cases, male partner is infertile. In 10-15% of the couples who are unable to conceive, both the partners are diagnosed with infertility. Whereas, 5-10% of the cases are of unexplained infertility i.e. the cause of the problem remains unexplained.
IUI (Intrauterine insemination)
The semen is collected and then processed in the laboratory. The seminal plasma is discarded and the best quality sperms are harvested and kept in special culture media. The ratio of half to one ml of sperms are then artificially deposited into the uterine cavity with the aid of a thin catheter IUI.
The success rates vary from 10-20% per cycle depending on the cause of infertility. The best results are seen among patients with cervical factor and IUI using donor sperms. IUI success is usually low among patients with severely low semen counts - less than 10 million per mg.
On the whole, if 10 patients undergo IUI every month, one or two will become pregnant every month. In about 6 months time out of the ten patients who started treatment, 4 to 6 patients will become pregnant. The rest would have to be treated with advanced procedures such as IVF or ICSI to achieve pregnancy.
IVF – IN VITRO FERTILIZATION
IVF is useful in treating unexplained infertility, endometriosis, failed IUI etc. This procedure includes removal of eggs from vagina, which are attached with ultrasound probe, and they will be mixed with the sperms of donors or husband, before keeping them in incubator for two days. After two days selected fertilized egg (embryo) is transplanted into the uterus (womb) of the female.
Step By Step Guide to IVF
Consultation with a fertility specialist is the primary step before going for the treatment. We at Fortis Bloom understand that infertility problems can be emotionally distressing, and hence we respect your situation and help you overcome it. First step of consultation leads to the understanding of problems and a brief guided outlook of the right treatment procedures.
A complete assessment of the associated problem is necessary before undergoing any treatment. Hence, the experienced team at Fortis Bloom prefers to conduct some investigations to track your reproductive health. The investigation procedures include routine blood tests, specific test to assess ovarian reserve, ultrasound pelvis and semen analysis.
The best way to deal with stress due to infertility is through counseling, which is suggested as a solution to the patients. We understand what patients are going through and we put forward the best way to reduce emotional stress over the subject. Counselors deal with patients to take out their fears and help them to relax beforehand.
4. Revision of your reports
Next step includes the revision of your reports by specialists to decide the procedure to be used for the treatment, and then a brief discussion over the protocols to be used. Before the ART cycle starts, our counselor will advise you to undergo some surgeries like laparoscopy/hysteroscopy before coming to the conclusion.
5. Starting the treatment
Regulations to control the hormonal level starts on 21st day and to maintain the down regulation of hormones you need to take 7-14 injections, which suppresses the hormonal levels that exist during the normal time. After accomplishing the task of down regulating hormonal level, stimulation procedures starts, which are checked with the help of USG or blood tests. Sometimes these down regulating procedures are not needed and your fertility specialist decides this.
Once the down regulation is achieved, which is done with the help of hormonal tests or by 2nd and 3rd day of periods, an ultrasound is carried out as a baseline for this procedure.
7. Egg collection
After 34-36 hours of trigger injection eggs are collected by giving mild anesthesia to the patient. This procedure is performed by using trans-vaginal scan, a procedure in which a needle, with attached probe, punctures the follicles via vagina. A negative pressure is then maintained to fetch the eggs and fluid, which then transferred to the IVF lab for further procedures. This procedure only takes 30 mins and the patient will be discharged after 4-6 hrs.
8. Sperm collection
The day when eggs are collected, the partner of the female donates fresh semen sample needed for further procedure. If the case is of male infertility, then the donor sperms are used. After collection of semen it is washed so that to separate the sperms and seminal fluids. The option of sperm freezing is also available at Fortis Bloom wherein the male partner can donate the semen sample beforehand, in case he will not be available to do it on the same day.
After the collection of sperms and eggs, the specialists at Fortis Bloom will use specific technique for the fertilization procedure. Afterwards, the sample is being stored in incubator for future use. Incubated eggs are kept undisturbed for 18-24 hours with regular checks under microscope for proper fertilization. The egg which gets fertilized and starts to divide is then known as the embryo. Embryo cells divide and have four to eight cells in them after 2-3 days of growth. This is the time when specialist checks the viability of embryos to be used for procedure by grading them according to the standards. Now is the time when you will be informed about the status of embryo and decision of fertility specialist over embryo transfer.
10. Embryo transfer
Now is the time when selected embryos are transferred to catheter and then are transferred into the uterus with extreme care. This whole procedure is monitored by using ultrasound technique, which uses vaginal route. This step ensures the acceptance of embryo and hence is an important and crucial step of an IVF program. Procedure can be of little discomfort, and hence after resting for 20 minutes, one can go home. The maximum number of embryo transferred in single procedure is three embryos. In exceptional cases if a good quality embryo is seen, then that is stored in frozen state for later use.
11. Post transfer care
Initial 14 days after the embryo transfer are the crucial ones, as during this time embryo attaches to uterus. To make this process a little more relieving few medications are prescribed with detailed description from specialist. You can do your routine work even after the procedure, as there is no compulsion that you have to take bed rest.
Pregnancy test is done after 14 days of embryo transfer. If the test comes positive then it gives the confirmation of pregnancy and you can meet up with your doctor for future guidance on this stage. After 7-10 days, regular ultrasound procedures are done to check the pregnancy stage.
If due to some unseen circumstances procedure failed and test result comes out to be negative then you have to stop medication with immediate effect and you have to keep track of your periods. This can be disappointing but a consultation with doctor about the failure is necessary, as you will be told for future course to be followed.
ICSI – INTRACYTOPLASMIC SPERM INJECTION
ICSI was serendipity when happened in 1992, but yet effective in treating male infertility. It was until 1990s when males with low sperm count (less than 5 million per ml) or poor sperm quality were not able to father children. The reason behind this was the traditional IVF technique, which works on the fusion of sperms with fertilized egg that is a rare event in case of low sperm count, as only one sperm will be able to penetrate the egg and if the number of sperms are low the chances reduces gradually.
However, with ICSI, single sperm can be injected by handling the fertilized egg in-vitro, which enables the use of single viable sperm.
Candidates for ICSI
ICSI is likely to be recommended if the male partner has:
- A very low or zero sperm count
- A high percentage of abnormally shaped sperm, or sperms with poor motility
- Ejaculatory dysfunction due to spinal cord injury or malfunction such as quadriplegics or paraplegics
- Retrograde ejaculation (ejaculation of the sperm into the urinary bladder) who’s partner fails to get pregnant with IUI
- Patients where fertilization has failed with In Vitro Fertilization
ICSI for men with zero sperm counts
Azoospermia in males, i.e. where there is no sperm present in the semen, can be because of two reasons. It can either be of the obstructive type where there is production of sperms in the testis but blockage of the conduction system, which brings the sperm out into the semen. Alternately, the azoospermia may be of the non-obstructive type, where there is a failure of the testes to produce sperms. In both these cases sperms can be extracted either from the Epididymis, in a procedure known as percutaneous epididymal sperm aspiration (PESA), or Testicle, in a procedure known as testicular sperm aspiration (TESA).
Sometimes when these don’t yield sperms then a biopsy of testicular tissue is taken, which sometimes has sperm attached. This is called testicular sperm extraction (TESE) or micro-TESE, if the surgery is carried out with a microscope.
Steps in ICSI
Most of the steps in ICSI are similar to a standard IVF which include:
- The woman is given injections called gonadotropins to produce many eggs
- The egg growth is monitored by vaginal sonography and serial Estradiol hormone estimation
- Once the leading follicles are 18 to 20 mm in size, a trigger injection of HCG is given
- The oocyte or egg retrieval is then done under short general anesthesia 35 to 37 hours after HCG injection
- The eggs are than identified from the fluid in a laboratory
- Sperm collection and processing in the lab. In case of azoospermia (no sperms in the semen), the sperms are collected directly from the testis with the procedures of PESA/MESA/FTNB/TESE or TESA
- The eggs are than dissected from surrounded material and healthy mature eggs are identified and placed into small droplets of culture media under oil
- The sperms are also placed into small droplets of PVP under oil and immobilized with a microinjection needle and aspiration of the immobile sperm into the needle
- The sperm is then injected into the egg and following that, they are placed in an incubator to provide them an optimum environment to fertilize and grow to form embryo
- Of these embryos 1, 2 or 3 good quality embryos are selected depending upon the clinical history and age of the patient
- These embryos can be transferred after 2 (four cell embryo), 3 (six-eight cell embryo) or 5 (blastocyst stage) days. If all goes well, an embryo will attach to your uterus wall and continue to grow to become your baby. After about two weeks, you will be able to take a pregnancy test
How long does ICSI treatment last?
One cycle of ICSI takes nearly four to six weeks for completion. Most of the treatment is an outpatient-based treatment requiring 4-6 hours admission only on the day of egg retrieval.
The success rate for ICSI is higher than conventional IVF methods. A lot depends on your particular fertility problem and your age. The younger you are, the healthier your eggs usually are, and the higher your chances of success.
IMSI (Intracytoplasmic morphologically selected sperm injection)
As a new breakthrough in treating male infertility, a new microscope machine allows infertility specialists to pick the best quality sperm while carrying out the specialized test-tube baby procedure of ICSI. IMSI helps magnify the image of the sperm 7,200 times, thereby allowing doctors to pick the best looking healthier sperms. We at Fortis Bloom IVF Centre at Fortis LaFemme Hospital, are using this technique to enhance and maximize results. The machine is an advanced version of the earlier technique of Intracytoplasmic Sperm Injection (ICSI), having the magnification capacity 16 times higher than ICSI.
In ICSI technique, an egg is held and injected with the husband's sperm, with the help of a machine called micromanipulator. If the husband has no sperms, then sperms are obtained by doing a testicular biopsy. The fertilization occurs outside the woman's body. The baby / embryo is created outside the body of the mother and then placed inside the mother's womb. The IMSI method was first developed in 2004 by a team led by Benjamin Bartoov, of Barilan University in Israel, who used IMSI to select those sperms with a shape and size that indicated good genetic quality. The pregnancy rate in patients jumped from 30% to 66%.
IMSI helps improve the success rate among men with the worst prognosis and is said to be more beneficial than ICSI in patients with previous two IVF or ICSI failures. It is also useful in couples with unexplained infertility. It has been shown that IMSI resulted in better egg fertilization rates, better quality embryos, better rate of blastocyst formation and therefore better pregnancy rates.
This technique was discovered in order to minimize the chances of multiple pregnancies, which can occur, by IVF technique. This procedure also increases pregnancy rate as only few viable Blastocyst wibb are used during the procedure. Culturing of embryos is done for 3 days initially, which is the cleavage stage (4-10 cells), before they are transferred to uterus. After extending the time of culture to 5-6 days, culture attains Blastocyst stage (up to hundred of cells). This is the time when embryologist do the selection of the most viable and potential embryo for implantation.
Blastocyst transfer may be appropriate for those patients who have:
- A better chance of having Blastocyst development (this will be determined by age and infertility conditions)
- Previous failed attempts at achieving a pregnancy
- Strong concerns about delivering high-order multiple pregnancies
It is important to consult with your doctor about whether blastocyst culture and transfer is for you.
Some couples are unable to conceive because of issues with the female eggs. These patients immensely benefit from egg donation. Egg donation is recommended for:
- Women with premature ovarian failure or menopause
- Women with poor quality eggs
- Carriers or women suffering from genetic disease, which can be transmitted to the offspring
- Women with recurrent abortions or recurrent IVF failures
In egg donation, a healthy young woman is selected, screened and then stimulated to produce multiple eggs, which are extracted and fertilized with the sperm of the recipient’s partner.
Selecting an egg donor
- Donor is typically a young healthy woman between the age of 21-and 30 years. Married women with normal and healthy children of their own, as egg donors are prefferred.
- Medical history of the egg donor is elicited and we screen them for all possible disorders like infections e.g. HIV, Hep B, Hep C, Syphilis, genetic screening and thalassemia screening is also done.
- Counselors do psychological screening of all egg donors.
- Process of matching: These egg donors are matched with the recipient and we try to match the physical characters like height, complexion, hair color, eye color, and skin type and last but not the least the ethnicity.
- Patients are also given an opportunity to select the donor on the grounds of social and educational background.
How does the cycle work?
Once we have finalized the donor, the next step is to synchronize the patient’s and the donor’s menstrual cycle. We then start stimulating the donor to produce egg and simultaneously we start the medicines for the recipient to develop the lining of the uterus, which enables the embryo to implant.
Once the egg is mature, oocyte aspiration is done and then fertilized with the partner’s sperm of the recipient, and the embryo is transferred in the uterus of the patient after 2-3 days.
The chances of conception in egg donation cycle at our centre is 40-50% per attempt. It is an excellent tool to help women with egg problem to fulfill their dreams of motherhood
Surrogacy is a viable option for the couples in which mother is unable to give birth to a child due to some medical or undesirable medical grounds.
In traditional surrogacy, the surrogate mother provides the oocyte as well as the uterus to foster pregnancy. However, in IVF surrogacy (otherwise known as ‘gestational surrogacy’ or ‘full surrogacy’), the surrogate mother carries a genetically unrelated baby produced by the gametes of the commissioning couple.
Indications for gestational surrogacy include:
- Conditions where the uterus is absent congenitally or after hysterectomy
- Patients with damaged uterus as in asherman’s syndrome, multiple fibroids etc.
- Recurrent abortions, Rh incompatibility or cervical incompetence
- Patients with repeated failure of IVF treatment
- Severe medical conditions where pregnancy can be life threatening like pulmonary hypertension
Recruitment of Surrogates
According to ICMR (Indian Council of Medical Research) the following guidelines have been laid down for the selection of surrogate mothers, which are strictly adhered to while recruiting these surrogates.
- Surrogate mother should not be more than 45 years of age. Before accepting a woman as a possible surrogate, it must be fully ensured that the woman satisfies all the testable criteria to go through a successful full term pregnancy.
- A relative, a known person, as well as an unknown person can act as a surrogate for the couple. In the case of a relative acting as a surrogate, the relative should belong to the same generation as the woman desiring surrogate.
- A prospective surrogate mother must be tested for HIV and should be seronegative for the virus just before the embryo transfer.
- No woman may act as a surrogate more than thrice in her lifetime.
- All potential surrogates undergo a complete work-up, which includes screening for sexually transmitted disease, basic endocrinological test, and ultrasound of pelvis. We as a routine perform hysteroscopy in a previous cycle for all women to evaluate the uterine cavity. The commissioning couple and the gestational carrier along with their spouses then undergo psychological and legal counseling with appropriate legal contracts.
Cycle Synchronization and Treatment Protocol
Both the commissioning mother and the surrogate mother are put on oral contraceptive pills in the previous cycle in order to synchronize their menstrual cycles. Ovarian stimulation is done using gonadotropins starting on cycle day–2. The dose is adjusted according to ovarian response, which is monitored by doing transvaginal sonographies and serum estradiol levels. HCG is administered when two or more leading follicles reached ≥ 18mm and oocyte retrieval is done under general anesthesia after 34–36 hours.
The gestational carriers undergo pituitary desensitization by a long acting GnRh analogue administered in the luteal phase of the previous cycle. All these then receive exogenous estrogen (estradiol valerate) therapy for endometrial preparation before the embryo transfer. Micronized Progesterone is added on the day of ovum pickup of the commissioning mother. On day 3 or day 5, embryo transfers are done. Post transfer luteal support is given to all the recipients in the form of estradiol valerate 6mg/day and micronized progesterone 600mg/day. ß–hcg test is done on day 14 post transfer to confirm pregnancy. If pregnancy is confirmed, luteal support is continued until 12 weeks of gestation.
A similar protocol for preparation of gestational carrier is used in case of frozen embryo transfer cycles. Micronized progesterone is started once the endometrial thickness and endometrial blood flow is adequate on sonography. Embryo transfer is subsequently done on day 3 or day 5 of starting of progesterone.