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Management of Infertility in Females

Dr. Umesh N. Jindal

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C. Assisted Reproductive techniques (ART)

ART refers to those procedures where gametes (sperm and oocyte) handling is done in-vitro or outside the body. The simplest of these is insemination and the more advanced techniques include IVF, GIFT and ICSI.

Artificial insemination (AI)

AI is done with husband or donor sperm depending upon the indication. Patency of at least one tube is required for this procedure to be successful. A fraction of motile sperms recovered after various methods e.g. density gradient, swim-up or percoll gradient are injected directly into the uterine cavity under aseptic precautions i.e. intrauterine insemination (IUI). IUI is done as close to ovulation (within 12 hours) as possible, judged by basal body temperature (BBT), home LH kits or most reliably, with ultrasound. Combining IUI with controlled ovarian hyper-stimulation (COH) to produce 2-4 follicles improves the results. Main indications include unexplained infertility, cervical factor, psychosexual problems, moderate oligospermia, early endometriosis, immunological infertility and with ovulation induction. COH with IUI have almost 15 ? 20% pregnancy rate per cycle as compared to IUI or COH alone which have success rate of 7 ? 10%. In severe oligospermia results are not as encouraging and the se cases should be better treated by ICSI. Recovery of active sperms less than 5 million/ml is a poor prognosticator. All sperm recovery techniques recover the motile fraction only. There is no way to improve, concentrate or enhance the fertilizing power of a given sample. Pooling of samples to get higher number of sperms does not improve pregnancy rate. Properly timed IUI is a safe, simple and useful technique when used in selected cases. The main risks are infection and cramps if adequate aseptic techniques are not used. In case sperm separation is not possible, intravaginal or intracervical insemination can be done.

Artificial insemination by donor sperm is generally done when the male partner has a cause of infertility which is not amenable to treatment by ICSI, or ICSI is not feasible or has failed. Donors are carefully selected, screened for sexually transmitted or genetic diseases, matched for blood group and other phenotypic characters of the male partner. Success ra te generally varies between 30 ? 40% per cycle with a cumulative pregnancy rate of 70 ? 80% over 3 cycles. Female partner needs thorough evaluation in case of failure or long standing infertility.

IVF – ET (In-Vitro Fertilization – Embryo Transfer)

In vitro fertilization and embryo transfer involves retrieval of oocytes, fertilization in laboratory and transfer of pre-embryos in the uterus after 2-5 days of culture in laboratory.  This includes following steps: Evaluation and selection of cases, Super-ovulation,Ovum retrieval, Embryo transfer, Pregnancy diagnosis and monitoring, Complications

Primary and absolute indication for IVF is bilateral tubal block. Choice between IVF and microsurgery depends upon the condition of tubes and extent of tubal damage, experience and facilities available. In general the balance has tilted in favor of IVF with gradual improvement in results as compared to those of microsurgery. Other indications include infertility of any etiology of long standing duration such as endometriosis, cervical factor, immunological causes, moderate male infertility, multifactorial and unexplained infertility, anovulatory infertility.

A complete infertility work up to assess all the problems is mandatory. The basic pre-requisite for selecting a case is presence of a normal functioning uterus, ability of ovaries to produce enough oocytes and retrieval of more than two million active motile sperms per ejaculate in the male partner. Next step is superovulation or a deliberate controlled induction of multiple follicles in normo or oligo-ovulatory women to recruit around 8-12 follicles. This is achieved by first down regulating the pituitary with GnRH-a and then stimulating with HMG or pure FSH. After at least 4 follicles of > 18 mm diameter are observed on USG, ovulation trigger with hCG is given. Ovum retrieval (OPU) is done transvaginally under ultrasound guided needle aspiration 34-36 hours after hCG. It is a simple procedure and has 60 – 80% oocyte retrieval rate in experienced hands.

The oocytes are incubated with washed spermatozoa and observed for fertilization after 18 and 48 hours for cleavage.

Up to four pre-embryos are transferred transcervically on day two or three after OPU. Currently, there is a trend towards blastocyst culture i.e. till day 5 post pick up and transfer of blastocysts is done. Culture of blastocysts helps in selecting best quality embryos and higher implantation rate. Success rates from 30 ? 50% are being reported. Main complications include a risk of hyperstimulation syndrome and multiple pregnancy. These can be kept to minimum with careful monitoring and planning. Other problems include high cost, time and inconvenience and psychological problems of undergoing long treatment and failure.

Pregnancy once conceived through IVF is like normal intrauterine pregnancy. It can have all other problems which a normally conceived pregnancy may have. There is no evidence of any increased risk of congenital malformations even in long term follow up of off spring.

GIFT (Gamete Intra-fallopian Transfer) – Gamete intra-fallopian transfer is a technique where oocytes after retrieval from the ovaries, either transvaginally or laparoscopically are transferred to the fallopian tube. A success rate of 25% – 30% has been reported. Normal function of fallopian tubes is an essential pre-requisite. Most centres have abandoned GIFT in favor of IVF because of obvious advantages. GIFT is done primarily because of religious beliefs when in-vitro handling of gametes is prohibited.

ICSI (Intra Cytoplasmic Sperm Injection) – Intracytoplasmic sperm injection is the latest technique in the armamentarium of ART specialists. The main indication is severe male factor infertility which include severe oligo-asthenospermia, obstructive azoospermia, maturation arrest (etc). Other indications include repeated IVF failures, idiopathic fertilization failure, immunological infertility or advanced age of female partners.

A single sperm is injected in an oocyte with the help of micromanipulator instead of leaving the oocytes and sperms together in a dish for fertilization. Rest of the procedure and problems are same as for IVF. Success rate comparative to IVF have been obtained with ICSI in those intractable conditions which were not amenable to treatment with IVF.

Ovum and Embryo donation – A gonadal, premature ovarian failure or post-menopausal women with intact functioning uterus can also conceive through this technique. A uterus which responds to exogenous hormones can be prepared for implantation. Oocytes donated by known or unknown donors can be fertilized and embryos transferred in prepared uteri. These pregnancies need exogenous hormonal support for first three months till the placenta takes over. Afterwards these pregnancies behave like all other normal pregnancies.

Cryopreservation – It is possible to cryo-preserve supernumerary embryos and transfer these at a later date. Successful cryo-preservation programmes have improved pregnancy rates per retrieval.

Psychosocial Aspects

The discovery of infertility can provoke a complex psychosocial crisis in either or both members of an infertile couple. The crisis involves an interaction between the physical conditions predisposing to infertility, the medical interventions addressing the problems, social assumptions about parenthood, the reaction of others and individual psychological characters. The process of diagnosing and treating infertility has a profound impact on the lives of affected couples. Education, guidance and counseling of couples go a long way in reducing the stress.

Dr. Umesh N. Jindal

Consultant Gynaecologist,
Gynae and Fertility Research Centre and IVF Clinic,
CMC, Sector 17-C, Chandigarh.

Consultant Gynaecologist, Gynae and Fertility Research Centre and IVF Clinic, CMC, Sector 17-C, Chandigarh

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