WHAT IS

IVF

Information Booklet for Public

Edited by: Dr Poonam Goyal | Dr Bhavana Mittal | Dr Sowjanya Aggarwal

What is IVF?
Information Booklet for Public

Edited by: Dr Poonam Goyal Dr Bhavana Mittal Dr Sowjanya Aggarwal

Crosslay Society for Promotion of Medical Education & Research

W-3, Sec-1, Vaishali, Ghaziabad-201012, NCR-Delhi Tel.: 0120-4173000, 4188000 Fax: 0120-4188199 E-mail: info@pch.co.in Website: www.pch.co.in

Foreword

At 11.47 pm on 25 July 1978, the world's first IVF baby was born in the United Kingdom. Thirty four years later, many thousands of infertile couples have been blessed with a baby worldwide. How many of us know that an average couple's chance of conception is only 20 %? Modern medicine has increased this possibility to about 50% after decades of research. However, this 50% is not applicable for everyone; it changes from patient to patient and also to a certain extent, from centre to centre. Though IVF does hold a lot of hope for couples, it is important to know all about it the pros and cons, as well as the realistic possibilities before opting for the treatment. Couples who approach an IVF centre come with a lot of emotional and psychological stress, which can be addressed with the information and knowledge this guide provides. This useful guide edited by Dr Poonam Goyal, Dr Bhavana Mittal, and Dr Sowjanya Aggarwal has explained the process of fertilization, infertility and the treatment options available in very simple language, without compromising on the quality of the matter. This guide will be a very useful resource for all couples and their families.

Dr K K Gopinathan HOD (Dept of OBG) & Unit Director - CIMAR Centre for Infertility Management & Assisted Reproduction A Unit of Edappal Hospital Pvt Ltd Edappal Kochi, Coimbatore
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Preface

The number of people with infertility has been gradually increasing over the years and it is estimated that one in every eight suffers from this disorder. Changes in lifestyle, social values and career goals have had an immense impact on the progression of this problem. However, since infertility is curable, an awareness of the causes and related treatment options is vital for any infertile couple. Pushpanjali Institute of IVF and Infertility is a modern Assisted Reproductive Technology (ART) centre with the latest technology in the field dedicated to helping couples with infertility. Our dedicated team of super specialist doctors, trained laboratory technicians, staff nurses and administrative staff provide holistic support to couples who come to us for solutions. This Guide What is IVF will be useful for such patients and their families. We hope that the guide will serve as a ready reckoner for all those seeking information regarding infertility disorders. In addition, it will also be of educational importance for all those individuals who value knowledge. We are grateful to Dr Vinay Aggarwal and Dr Vijay Agarwal for their guidance and unstinted support. Dr Gaurav Aggarwal needs a special mention for his continuous and valuable inputs. We are also thankful to Dr Madhumita Puri for her help and support in the compilation and editing of this Guide. Equally invaluable are the services rendered by Ms Tabassum in designing the book for which we are indebted; and also Ms Sini for her contribution. Editors Dr Poonam Goyal Dr Bhavana Mittal
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Dr Sowjanya Aggarwal

Contents

Page No. Introduction Help your treatment succeed Basics of human fertility - Ovulation, fertilization and implantation Intrauterine insemination (IUI) Fertility enhancing endoscopic surgery In-vitro fertilization (IVF) / Intracytoplasmic sperm injection (ICSI) l Indications l Egg production l Egg recovery l Insemination l Embryo transfer Outcome of IVF treatment Percutaneous epididymal sperm aspiration (PESA) and Testicular sperm extraction (TESE) Some common issues of concern Other treatments l Egg, Sperm and Embryo donation l Sperm donation l Egg donation l Embryo donation l Surrogacy 1 2 3 4 5 6

1. 2. 3. 4. 5.

6. 7. 8. 9.

10 11 12 14

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Introduction

Welcome to Pushpanjali Crosslay Hospital; and the Pushpanjali Institute of IVF and Infertility! This booklet explains the treatments we provide and, hopefully will answer many of your questions. However, in case of any doubt or concern, please contact the staff. We understand the anxieties surrounding infertility and its treatment and hence will support you and keep you informed about the progress of your treatment.

Please read this booklet carefully as IVF and associated treatments are complex, and the more you understand before treatment starts, the better.

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Help Your Treatment Succeed

Watch your weight The chance of becoming pregnant is increased when women are the correct weight for their height.

Stop smoking Smoking can damage eggs and sperm.

Eat and drink healthy Eat a well-balanced diet, and start taking 400g folic acid daily.

Basics of Human Fertility - Ovulation, Fertilization and Implantation

Ovulation: With natural conception, a single egg develops in one of the ovaries each month. It grows in a fluid-filled cyst (follicle) for about two weeks before it is released this process is known as ovulation. Fertilization: After sexual intercourse, the egg enters the fallopian tube and meets the sperm. Fertilization creates a fertilized egg or embryo. As the embryo passes down the tube to the womb (uterus) its cells divide and grow. Implantation: If the embryo implants in the lining of the uterus (the endometrium), a pregnancy is established approximately one week after ovulation. The developing follicle produces a hormone (Estrogen). Estrogen levels can be measured in the blood, and follicles can be seen using ultrasound scanning. After ovulation, the follicle is transformed into a structure known as a corpus luteum, which produces the hormone progesterone as well as Estrogen. These hormones help support the lining of the womb and any developing pregnancy.

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Intrauterine Insemination (IUI)

Induction of ovulation In this treatment, gonadotropins stimulate the ovaries to produce between one and three eggs. This treatment is used for women who fail to produce eggs but have normal tubes and whose partner's semen is normal. The injections usually continue for two weeks. The ovarian response is monitored by ultrasound scans and blood tests. Once the scan and blood tests suggest a mature follicle(s), you will be advised to have intercourse/IUI. If too many follicles grow, treatment is stopped and it is essential that you use condoms during sexual intercourse. Intrauterine insemination (IUI) using donor or partner's semen With IUI, specially prepared samples of semen are inseminated into the womb using a fine tube passed through the cervix. This is not painful and is carried out by our doctors. We carry out ovarian stimulation in addition to IUI for many couples with unexplained infertility. We offer IUI alone for couples with coital or ejaculatory disorders. We also use IUI for couples requiring donor sperm insemination.
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Fertility Enhancing Endoscopic Surgery

Laparoscopy Laparoscopy is a surgical procedure that involves making very small cuts in the abdomen, through which the doctor inserts a laparoscope and specialized surgical instruments. You may be advised laparoscopic surgery to help in diagnosing a cause for infertility. Some causes of infertility, like endometriosis, can only be diagnosed through laparoscopy. Laparoscopy allows your doctor to not only see what's inside your abdomen, but also biopsy suspicious growths or cysts. Also, laparoscopic surgery can treat some causes of infertility, allowing you a better chance at getting pregnant either naturally or with fertility treatments. Hysteroscopy Hysteroscopy is designed to allow the doctor to view scar tissue, polyps, fibroids, and other defects located inside the uterus. Common Conditions Treatable with Hysteroscopy Endometrial (Uterine) Polyps Fibroids in the Uterine Cavity Scar Tissue Uterine Septum
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In-vitro fertilization (IVF) / Intracytoplasmic sperm injection (ICSI)

Indications for IVF /ICSI Tubal factor infertility Unexplained infertility Male factor infertility - Total motile sperm count< 1 million - <4% normal morphology and TMC< 5 million - No or poor fertilization in the first IVF cycle when T MC <10 million - No or poor fertilization in two IVF cycles when TMC > 10 million - Epididymal or testicular spermatozoa Endometriosis Cervical / Immunological factor Hormonal disturbance In-vitro fertilization (IVF) breakthrough in the late 1970s was the most important advancement made in treating infertility. IVF or the test tube baby technique literally means that fertilization is made to take place in a glass (vitro) dish or crucible. However, since the recent past, plastic crucibles are used rather than glass ones, and in vitro now refers to any procedure taking place outside the body. In IVF treatment, eggs are removed from the ovary just before ovulation. The eggs and sperm are put together in a dish. If fertilization occurs, the embryo is
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cultured in an incubator and placed in the womb two or five days later. If a pregnancy is achieved, the pregnancy continues naturally. IVF and its developments are widely used to treat male and female disorders. IVF is divided into four main stages:
l l l l

Egg production Egg recovery Insemination and fertilization Embryo transfer

Egg production The chance of pregnancy is increased if more than one egg is recovered. Initially the function of the ovary is suppressed using a drug called GnRH agonist. The ovary is then stimulated with another drug called gonadotrophins. The drugs are injected just under the skin, which rarely cause soreness. Most women administer the injections themselves after training from our nurses. GnRH agonist injections begin approximately one to two weeks before the start of a period. Gonadotrophin injections are administered when that period starts. The GnRH agonist and gonadotrophin injections together continue for another 10-12 days until you are ready for egg collection. We routinely use this long treatment protocol. We may increase or decrease the dose of drugs as you undergo treatment, depending on the results of your blood tests and scans. Blood tests during the period of stimulation are carried out to measure the level of estrogen in the blood, to ascertain ovary response and to check for
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excessive response. Ultrasound scans using a vaginal ultrasound probe are carried out to measure the size of the developing follicles. Vaginal scans do not hurt and does not require a full bladder. Egg recovery Egg recovery is carried out under anesthesia and most women do not recollect the egg recovery operation because of the drugs used. Eggs are recovered by needle aspiration under vaginal ultrasound guidance. Laparoscopic egg recoveries are only necessary in exceptional circumstances when it not possible to use the vaginal route. You will be admitted to the hospital ward for half a day. Do not eat anything after midnight.

A single human egg surrounded by cumulus cells

Insemination and fertilization The male partner provides a sperm sample on the day of egg recovery (unless you are using frozen sperm). After egg recovery, the most active and normal sperm are added to the eggs. The eggs and sperm are incubated overnight and checked the next morning for signs of fertilization. After the fertilization check, the embryos are left in the incubator to develop Two or three days after egg recovery, the best one or two embryos are placed in
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the womb. These embryos are called early cleavage (EC) embryos. Any remaining EC embryos of good quality may also be frozen.

Day 2 Two 4 cell embryos

Day 3 8 cell embryo

Embryo transfer The number of embryos to be placed is made individually on the day of transfer. Usually one to three good quality embryos is placed in any one cycle. The remaining good quality embryos can be frozen for use in the future. After embryo replacement you will be given another injection or hormone pessaries to support the lining of the womb. Before you go home, you will receive a date for a blood test to confirm pregnancy. During this time, you should not do any strenuous activity or have unprotected intercourse until the outcome of treatment is known. Frozen embryo placement cycles One or three frozen/thawed embryos are may be placed in each cycle, the details of which will be discussed with you. Embryos are thawed before placement and the best one or three embryos are selected for placement. Frozen/thawed embryos are placed in a cycle controlled by drugs. This involves GnRH agonist injections, followed by oestrogen tablets and progesterone vaginal pessaries.
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ICSI Intracytoplasmic sperm injection (ICSI) is a refinement of the IVF technique and offers hope to men with sperm problems and couples with suspected fertilization defects. If the sperm fails to fertilize the egg naturally or during IVF, this is usually because the sperm fails to penetrate the egg's outer and inner membrane.
Egg Sperm

Egg

Micro-injection Sperm

Conventional IVF

Intracytoplasmic sperm injection (ICSI)

With ICSI, eggs are collected from the woman and sperm from the man in exactly the same way as in IVF. After egg recovery, a single sperm is injected with a tiny needle directly into the egg. Approximately one in five eggs is not mature and cannot be injected. Approximately one in ten eggs which are injected will not survive. If fertilization occurs, the embryos are replaced as in standard IVF.
A mature egg being injected with a single sperm

In current day scenario, most of the ART consultants prefer to do ICSI for all patients in order of overcome fertilization defects and have better results.

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Outcome of IVF Treatment

IVF and associated treatments have a limited success rate. Approximately a fifth of IVF pregnancies may result in miscarriage after a positive pregnancy test, a similar proportion as following natural conception. Over one million babies have been born from IVF worldwide with no indication of major health problems. There is no evidence that babies born after frozen embryo replacement have an increased rate of abnormality.

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Percutaneous Epididymal Sperm Aspiration (PESA) and Testicular Sperm Extraction (TESE)

PESA and TESE techniques are used when sperm is produced in the testes but the sperm cells cannot enter the seminal fluid. With TESE, the sperm is extracted directly from the testis and with PESA it is aspirated from a tube lying next to the testis. The decision to use TESE or PESA will depend on the diagnosis. The sperm is then injected into the egg using ICSI.

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Some Common Issues of Concern

Screening All couples accepted for treatment are tested for syphilis, hepatitis B and C and HIV. To minimize the risk of embryos contaminating other embryos in the containers, treatment is only offered when both partners are negative to viral screening. If you are found to carry one of these viruses, possibility of treatment at another unit will be discussed. Treatment cycle The treatment cycle starts when you begin injections of gonadotrophins, and is only considered to be complete after all embryos created during an egg recovery cycle have been replaced. One cycle may therefore involve several embryo replacements. Labeling eggs, sperm and embryos in the laboratory All samples are labeled with your name and hospital number. These details are always checked against your hospital notes. In the laboratory, all containers have your name and details written indelibly or etched on them. All procedures eg, preparation of sperm is carried out for only one couple at a time and are witnessed by two embryologists. All frozen embryos are stored individually and labeled permanently with your full details. Possible complications IVF and its associated treatment can involve certain complications. There are
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two main risks - multiple pregnancy and ovarian hyperstimulation syndrome (OHSS). Multiple pregnancy Generally, only two to three embryos are transferred. Twins are more common approximately 20% of all pregnancies. Multiple pregnancies have many more complications than a singleton pregnancy. Premature birth is the most significant, since babies born too soon may not survive or have serious lifelong disabilities. A multiple pregnancy also carries greater risk for the mother. Ovarian hyper stimulation syndrome (OHSS) In about 7% of cases, ovarian hyper stimulation can occur after the ovaries have been stimulated for IVF. The severe form may have life threatening implications. The ovaries swell and become painful and the high estrogen levels cause nausea and vomiting. Fluid accumulates in the abdomen and sometimes around the lungs. A small number of women less than 1% - will have severe symptoms and require hospital admission. We monitor for OHSS throughout treatment and if your ovaries show excessive response, the cycle may be cancelled. Sometimes, it is possible to recover and inseminate your eggs and freeze the resulting embryos. The embryos can be replaced two to three months later when symptoms have settled. Ovarian cancer There have been reports that repeated ovarian stimulation increases the risk of ovarian cancer, although no link has been proven. Women who have never conceived have a higher risk of ovarian cancer. Women who conceive after ovarian stimulation appear to carry the same risk of ovarian cancer as those who conceive naturally.
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Other Treatments

Egg, Sperm and Embryo donation Some couples may need to consider the use of donated eggs, sperm or embryos. Deciding to undergo treatment using donated eggs, sperm or embryos will raise personal issues and requires careful consideration. Sperm donation Sperm donation may be offered to couples with a sperm disorder or those with a high risk of passing on a serious genetic disorder. Our sperm donors are carefully chosen, healthy men aged from 18 to 40, all of whom are screened for Hepatitis B and C, HIV. We try to match the donor with the male partner as closely as possible, with similar skin complexion, race, height, hair and eye color. Donor insemination can either be used alone or in conjunction with other procedures like IVF. Egg donation Egg donation is an option if the woman is a known carrier of a serious genetic disorder or when her ovaries are absent, have ceased to function or are unlikely to respond to induced ovulation.

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Couples referred for egg donation will have a consultation and assessment before treatment. The donor and her partner are also counseled. The donor undergoes a cycle of ovarian stimulation as described above. Embryo donation Donated embryos can be offered to couples who have neither eggs nor sperm. Surrogacy Surrogacy is an arrangement in which a woman carries and delivers a child for another couple or person. The intended parent or parents, sometimes called the social parents, may arrange a surrogate pregnancy because of homosexuality, female infertility, or other medical issues which make pregnancy or delivery impossible, risky or otherwise undesirable. The sperm or eggs may be provided by the 'commissioning' parents, but donor sperm, eggs and embryos may also be used.A gestational surrogacy requires the implantation of a previously created embryo, and for this reason the process always takes place through In Vitro Fetilization (IVF). If the surrogate receives compensation beyond the reimbursement of medical and other reasonable expenses, the arrangement is called commercial surrogacy, otherwise it is often referred to as altruistic surrogacy. The legality and costs of surrogacy vary widely between jurisdictions and is controlled in India according to ICMR guidelines.

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