Surrogacy is an arrangement whereby an intending couple commissions a surrogate mother to carry their child.
Infertility has been an age-old problem, persisting all over the world. Many people have had problems conceiving because of reasons as small as that of illiteracy. In this modern era of advancement in the field of science, particularly medical science, conception has become more achievable than it was ever.
The utmost important step in treating infertility is identifying the cause. Once the cause has been identified, then conception can be made possible by various medical procedures and treatments such as those in assisted reproductive techniques. To understand these treatment options, we need to first understand how the normal physiology of conception works and what could go wrong with it.
- 1 Conception and its Normal Physiology:
- 2 Infertility:
- 3 Tests of Ovulation:
- 4 Artificial Insemination(AI)
- 5 Assisted Reproductive Technology:
- 5.1 Investigations required to be done before ART:
- 5.2 Principle Steps in ART Cycle:
- 5.3 Types of ART Procedures in Practice
- 5.4 Indications of ICSI in male infertility comprise:
- 6 Surrogacy:
Conception and its Normal Physiology:
Conception results from fertilization of the ovum (egg) by a spermatozoon (sperm). The sperm cell is formed in the testes (testicles) in the male and is ejaculated into the female reproductive tract (posterior fornix of the vagina) during the act of coitus.
The sperm is motile and then travels from the vagina through the cervix into the uterus and then to the fallopian tubes. On the other hand, the egg cell is released from the ovary on the 14th day before the next period due to the hormonal orchestra, which is presided over by the pituitary and the hypothalamus.
The egg is then fertilized in the fallopian tube, and it is now called a zygote. Zygote matures into an embryo in 5-6 days. This embryo then gets implanted into the wall of the uterus, where it grows by acquiring nutrition from the mother by means of placenta.
Failure of a couple to conceive is termed as infertility. If a couple fails to achieve pregnancy after 1 year of unprotected and regular intercourse, it is an indication to investigate the couple. It has been observed that 80% of normal couples achieve conception within a year.
The causes of failure to conceive may be due to anomalies in either of the partners. In one-third of all cases, the male partner is responsible, in the other one-third, the female is at fault, and the rest hold both the partners at fault.
The causes for infertility in both sexes have been mentioned superficially in the table given below.
Image of the Female Reproductive Tract.
|Infertility Causes in Male||Infertility Causes in Female|
|Disorders of spermatogenesis||
Dyspareunia and vaginal causes.
|Obstruction of the efferent ducts||Congenital defects in the genital tract.|
|Obstruction of the efferent ducts||Infection in the lower genital tract.|
|Accessory gland disorders||Cervical factors.|
|Disorders of sperm motility||Uterine causes.|
|Disorders of sperms and vesicular fluid||Tubal factors.|
|Unexplained||Peritoneal causes—adhesions, endometriosis.|
|Psychological and environmental factors such as smoking, alcohol consumption, tobacco chewing, diabetes and drugs
||Chronic ill-health—especially thyroid dysfunction.|
|Obesity||Hormonal—pituitary gland dysfunction,, and hypothalamic disorders|
As stated before, finding out the cause of infertility in a patient is essential. Hence, further, we will see in brief what investigations are to be undergone for the same.
Before starting investigations, it is necessary to inquire about the coital history regarding the time and frequency of it, about various addictions, etc. Further general examination of the body and the reproductive organs is done to detect any gross abnormalities if present.
Infertility investigations for males include the following:
- Semen analysis.
- Hormonal assays.
- Testicular biopsy—for histology, genetic study, and cryopreservation in assisted
- reproduction (intracytoplasmic sperm insemination).
- Immunological tests
- Patency of vas
- Chromosomal study
For the time being, we will shift our focus on to female infertility and its management. Let’s start with the various investigations required for finding the cause of infertility in a female. To make it simple, let’s present it with respect to the causes stated in the aforementioned table.
Uterine, Tubal, and Peritoneal factors:
- These tests basically help in visualizing the reproductive tract from the inside for a better understanding of factors such as patency.
- Hysterosalpingography (HSG)
- Laparoscopy and chromopertubaton
- Hysteroscopy and Falloscopy
- Ampullary and Fimbrial salpingoscopy
Tests of Ovulation:
These tests check the process of ovulation and whether there is a pressure of any factor that may hinder the normal process.
- Basal Body Temperature
- Endometrial biopsy
- Fern test
- Hormonal study: Plasma Progesterone levels, Luteal phase, LH/Prolactin/FSH levels, Thyroid tests
- Immunological tests
All these tests are not necessarily to be done since these are very costly, and doing all would be a waste of energy and resources. It may get very annoying for the patient to undergo a whole bunch of tests. Hence these tests are to be approached in a stepwise manner, one after the other until the anomaly has been detected.
Most anomalies found in the above tests are treatable. Such as most tubal blockages can be resolved surgically, hormonal imbalance can be treated with appropriate drugs or hormone replacement therapy.
Different methods are :
- IUI—Intrauterine insemination
- Fallopian tube sperm perfusion.
Intra-Uterine Insemination (IUI):
lUI may be either AIH (artificial insemination husband) or AID (artificial insemination donor). Husband’s semen is commonly used.
The purpose of IUI is to bypass the endocervical canal, which is abnormal and to place the increased concentration of motile sperm as close to the fallopian tubes. The indications are:
- Hostile cervical mucus
- Cervical stenosis
- Oligospermia (low sperm count) or asthenospermia (reduced sperm motility)
- Immune factor (male and female)
- Male factor—impotency or anatomical defect (hypospadias) but normal ejaculate can be obtained
- Unexplained infertility
Common methods to extract sperm from the seminal plasma are washing, swim-up, and density gradient centrifugation. The count for insemination of the processed motile sperm should be at least 1 million.
Best results are obtained when the motile sperm count is above 10 million. Oocyte survives only for 12–24 hours whereas normal sperm survives in this female reproductive tract and can fertilize an egg for at least 3 days. The procedure may be repeated 2–3 times over a period of 2–3 days.
Timing of IUI:
In cervical insemination, timing is not so vital because the sperm can survive in the cervical canal for a day or two. As the reservoir function is not available in lUI, some form of controlled ovarian hyperstimulation (COH)is required.
Results: Cumulative conception rates after 12 insemination cycles are 75–80%.
Assisted Reproductive Technology:
ART refers to any fertility treatment in which the sperm from a male and egg from a female are manipulated outside the body to produce embryos and achieve conception.
The most common indications for ART are cervicovaginal pathology (e.g., thick mucous) and tubal etiological factors (tubal blockages and adhesions) in females and azoospermia (complete absence of sperms in the seminal fluid) in males.
Investigations required to be done before ART:
- Maternal age of more than 40 years, the success rate drops considerably
- Serum FSH and Serum estradiol on day 3 of the cycle (Female hormones essential for conception)
- Thyroid function tests, diabetes.
- Test for ovarian reserve: It gives a measure of viable eggs present in the ovaries. This is indicated in women over 35 years of age, smokers, the presence of only one ovary and unexplained infertility.
- Test for infections such as STDs and HIV
- Immunological tests for anti-sperm antibodies in both partners.
- Assess uterine cavity—HSG/hysteroscopy/transvaginal sonography.
- Complete seminogram and treatment of the male partner prior to the ART procedure.
- Diagnostic laparoscopy to assess tubal patency and treat any subtle causes of infertility such as lysis of adhesions, treatment of endometriosis (fibroids), etc.
Principle Steps in ART Cycle:
1- Down-regulation using GnRH agonist
Drugs used for down-regulation of the pituitary gland to prevent premature ovulation
2- Controlled ovarian hyperstimulation (COH)
Done with the help of stimulating drugs.
3- Monitoring of follicular growth
The follicular growth response is monitored by various tests, and when the favorable numbers are achieved, human chorionic gonadotropin (hCG) hormone is given intramuscularly. The oocyte is retrieved 36 hours after the hCG is given. hCG induces oocyte maturation.
4- Oocyte retrieval and obtaining sperms
Oocyte retrieval is done aseptically through vaginal route under ultrasound guidance.
The sperms are obtained by one of the following sources:
- Semen washing in a normal male.
- Testicular sperm aspiration (TESA).
- Percutaneous epididymal aspiration. However, a lesser number of sperms are available (PESA) with this technique. This technique can also cause trauma to the epididymis.
- Microsurgical epididymal sperm aspiration (MESA)—the tissue can be cryopreserved for future cycles or future pregnancy.
Cryopreservation avoids repeat aspirations, reduces the cost of the procedure, and can be used in subsequent cycles as well as for further pregnancies. Cryopreservation is also useful in young men who have to undergo surgery, radiotherapy, or chemotherapy for cancer, or are frequent travelers.
5- Fertilization in vitro (IVF, ICSI, GIFT).
The sperm used for insemination in vitro is prepared and approximately 50,000 to
100,000 capacitated sperm are placed into the culture media containing the oocyte within
4–6 hours of retrieval.
6- Transfer of gametes or embryos.
The fertilized ova at the 6–8 blastomere stage are placed into the uterine cavity through the cervix(transcervically). Not more than three embryos are transferred per cycle to minimize multiple pregnancies.
7- Luteal support with progesterone
It is essential for maintaining pregnancy.
Types of ART Procedures in Practice
1- In-vitro fertilization (IVF)
The above steps are followed by fertilization. Then the embryos are then cultured for 3–5 days followed by subsequent transfer of selected fertilized oocytes transcervically under ultrasound guidance into the uterine cavity.
2- Gamete intra-fallopian transfer (GIFT)
This involves ovarian stimulation and egg retrieval, followed by laparoscopically guided transfer of a (unfertilized) mixture of two ova and 50,000 sperms into each of the fallopian tubes.
3- Zygote intra-fallopian transfer (ZIFT)
This involves the laparoscopic transfer of fertilized eggs (zygotes) on day 1 after fertilization into the fallopian tube.
4-Intracytoplasmic sperm injection (ICSI)
This technique aims at helping couples with severe male factor infertility. One sperm is directly injected into each mature egg, prior to the intrauterine transfer of the fertilized eggs i.e., fertilizing the eggs manually. The method yields 50–70% successful fertilization rates.
Indications of ICSI in male infertility comprise:
- A sperm count of less than 5 million/ml.
- Decreased or absent motility of sperms.
- Many abnormal sperms.
- Previous failed IVF.
- Unexplained infertility.
Lately, spermatids have been matured in vitro and utilized in ICSI.
- Ovum donation.
- Donor eggs are offered to women with poor egg numbers or quality and elderly women. An egg donor is screened for HIV and other diseases. Ovum donation is also required if both ovaries are removed or radiated.
- Ovarian transplant is a possibility in the future.
- Surrogacy and posthumous reproduction are extensions of ART procedures. However, ethical, legal, religious, and social issues of these procedures need clarification and understanding. Hysterectomised (surgical removal of the uterus) woman needs surrogacy.
- Stem cell culture agar is a future goal in infertility.
- Adoption. Looking at the cost and the stress involved, adoption can be a convenient option for infertile couples. Many, however, prefer to have their own genetic babies and resort to adoption when all other measures fail.
- Oocyte retrieval can cause bleeding trauma, infection, pain, pelvic abscess in females.
- Failure of the in-vitro fertilization.
- Ectopic and heterotropic pregnancy (pregnancy at a site other than the normal).
- Multiple pregnancies and complications
- Hyperstimulation syndrome.
- Abortion, Intrauterine growth retardation (IUGR).
- Premature ovarian failure.
- Breast cancer.
- Ovarian cancer—due to hyper-stimulation.
It is an arrangement whereby an intending couple commissions a surrogate mother to carry their child. It is known to be of two types:
In this type, the surrogate mother’s ovum is fertilized by the sperm of the intended male by natural ways or artificial insemination. Hence this helps to achieve genetic composition partially similar to that of the biological father.
Here the ovum from the intended mother and sperm from the intended father is obtained. The ovum is then fertilized by the sperm in-vitro (laboratory). Then the embryo is transferred into the uterus of the surrogate mother. Here the offspring holds complete genetic resemblance to the intending parents.
Surrogacy required is in:
- Absent uterus, diseased uterus.
- The general condition of the woman precludes pregnancy.
- Repeated pregnancy loss.
- Hereditary disease.
- Failed IVF.