Assisted Reproductive Technologies (ART)
The term ART is used to describe all the methods of artificially assisted conception and refers to several different methods designed to overcome barriers to natural fertilization. The earliest forms of ART were those designed to assist in cases of male infertility, such as assisted transfer of sperm into the vagina or uterus. Intrauterine insemination (IUI) is still widely used today, however mainly for specific cases. Since the first successful birth after IVF in the UK in 1978, many techniques have been developed and success rates have increased dramatically.
Today, ART is called upon for cases of infertility due to anatomical problems (e.g. blocked fallopian tubes), severe male factors (sperm defects, low sperm counts, male and female antisperm antibodies), widespread endometriosis and unexplained infertility. One of these techniques, in vitro fertilization (IVF) has now been widely practiced for more than 25 years and is the starting point for most ART treatments.
As in most patients ovulation is induced, luteal phase support either with pure progesterone or hCG is essential to improve the pregnancy rates.
Intravaginal insemination (IVI)
Intravaginal insemination, again a practice which has been used for some time, is now used for donor sperm procedures, artificial insemination partner (AIP) or artificial insemination donor (AID). IVI offers no benefits over normal sexual intercourse, in the case of AIP, but can be useful to circumvent male impotence.
Intrauterine Insemination (IUI)
In this fairly simple procedure, sperm is placed within the uterus around the time of ovulation. With the aid of an ultra sound scan the exact size, time and state of the ovarian follicles can be known. The semen is washed in a special media and then processed so that the most active and healthy sperms are available, leaving the dead sperm and other debris. This processed sample is placed into the uterus of the woman. Before IUI it is necessary to have abstinence of 3 – 5 days. Shorter abstinence may yield low counts, while a longer abstinence results in a semen sample with decreased motility.
And when the woman’s egg travels down her tubes on their own at the time of ovulation, these sperm fertilize it, as would happen naturally. The premise of IUI is that the sperm can reach and fertilize the egg more easily if placed in the uterine cavity. Ovulation induction combined with IUI is often the first course of treatments. IUI alone offers a good conception rate per cycle while combining ovulation induction with IUI may boost this rate. Gonadotropins combined with IUI offers a 25 -30% per cycle conception rate. (Rates worked considering minimal to mild tubal damage, normal to mild sperm abnormalities and women less than 40 years old.) Cumulative conception rate with 4 cycles of IUI is between 50 – 60 %. After 4 cycles the pregnancy rates drops down steeply, thus IUI is not recommended cycle after cycle if there is no conception in 4 – 6 cycles of IUI. These patients should then undergo IVF or ICSI depending on the etiology of sub-fertility.
The IUI process can be summarized in the following five steps
- Ovulation induction with clomiphene citrate,Letrazole or gonadotropins/ or use of natural cycle
- Follicular monitoring by trans vaginal ultrasound for follicular growth
- Induction of follicular maturation & ovulation by administration of hCG injection in dose of 5000 – 10,000 IU IM or GnRha in dose of 500 ug SC
- Collection of semen sample & processing in the seminology lab 36 hours after the injection. Semen takes 20 - 30 minutes for liquefaction, after which the sample is washed either by swim up technique or discontinuous gradient technique to isolate only the motile fraction from the sample to be utilized for insemination. The sample after washing is kept in CO2 incubator for an hour to initiate capacitation & acrosome reaction.
- USG done to look for rupture of follicle, which signifies ovulation. On ovulation the follicle either collapses thus results in decrease in size or there are internal echoes inside the follicle due to corpus luteum formation. If an USG is done within six hours of rupture free fluid is seen behind the uterus.
- The sperms are then inserted into the uterine cavity with the Teflon catheter.
- If the follicle has ruptured at the first scan i.e. 36 hours, single IUI is done. If it has not ruptured the IUI is repeated with the same sample kept in the incubator after 48 hours.
- The patient has to rest in bed for 1 hour after the procedure.
- Later she can perform her routine activities
- Luteal phase support is given either with pure progesterone or hCG or both to improve the success rate, as ovulation inducing drugs may result in luteal phase defect.
- Beta hCG is done 19 days after ovulation to confirm pregnancy.
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Advantages of IUI
- Minimally invasive
- Less emotional commitment
- Less time-consuming
Disadvantages of IUI compared to IVF-ET and ICSI
- Fertilization cannot be confirmed
- Risk of multiple pregnancy
- Tubes must be unobstructed
IVF - In Vitro Fertilisation
IVF or In Vitro Fertilization is often known as “the test tube baby treatment”. IVF treatment involves placing sperm and eggs together in a culture dish so that fertilization occurs in the laboratory. Not all the eggs will fertilize when mixed with sperm, so to increase your chances of success we stimulate the ovaries to produce several eggs at the same time. The success rate with this procedure is anywhere between 20 – 35 %. Different centers have different results & this depends basically on patient parameters & proper functioning ART lab, which should be well equipped, & equipments calibrated regularly for proper functioning & better results.
Cases in which IVF may be recommended
- Women with blocked or damaged fallopian tubes, where the egg may not be able to meet the sperm or make its way into the uterus.
- Couples where there is a problem with the sperm, i.e. the number of sperm is low, the sperm do not move well, or where there are high numbers of sperm, which are not properly formed.
- Women with ovulatory problems.
- Women with endometriosis.
- Cervical problems.
- Couples who have unexplained infertility.
- Failure of IUI
Advantages of IVF
- Fertilization is confirmed
- Successful treatment in most infertility cases
Disadvantages of IVF
- Technically demanding
- Risk of multiple pregnancy
- Price / costs
The IVF procedure at a glance
The IVF process can be summarized in the following five steps:
- The ovaries are stimulated with FSH, in order to cause ripening of several follicles. This is called controlled ovarian stimulation (COS). Successful COS requires very precise day-by-day adjustment of the hormonal dose. This can only be achieved with the use of FSH in combination with GnRH analogues – GnRh agonist or GnRh antagonist, allowing the continuous growth of a large number of follicles whilst preventing a spontaneous LH surge through the suppression the natural secretion of FSH and particularly LH. A premature LH surge can cause early ovulation and jeopardize the success of the treatment cycle;
- When ultrasound monitoring indicates that the follicles are large enough to contain an egg that has matured sufficiently, hCG is injected to induce final follicular maturation;
- The eggs are collected about 34 - 36 hours after the hCG injection. Egg collection is usually carried out via the vagina under ultrasound guidance utilizing a long hollow needle, although egg collection by laparoscopy (via the abdominal wall) may occasionally be used
- The eggs are then fertilized with the sperm and the first cell divisions are monitored.
- Embryos are transferred into the uterine cavity 2-6 days after in vitro fertilization. A full bladder is required for embryo transfer as it is carried out under ultrasound guidance, for correct placement of the embryos in the uterine cavity.
- A two-week wait for a pregnancy test
Usually, more than one embryo is transferred to increase the chance of a successful pregnancy. To avoid the risk of multiple births, it is generally recommended that a maximum of two to three embryos be transferred. In November 1999, the American Society for Reproductive Medicine (ASRM) released guidelines on the number of embryos to be transferred. Under British and German law, a maximum of three embryos can be placed in the uterus at one time, although there are no similar legal restrictions governing our country. The number of embryos transferred also depends on the age of the patient, cause & duration of infertility, previous failed treatments & quality of the embryo developed.
With the introduction of cryopreservation, excess embryos can be stored for future cycles thus avoiding the patient to go through ovarian stimulation and egg collection again. These stored embryos can be transferred in a natural or hormone replacement cycle. Post thaw survival of the embryos may not be 100 %.
Ultrasound guided oocyte aspiration with collection of eggs in a tube containing IVF medium
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What is done with the eggs & sperms in the Lab?
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How the eggs, sperms & embryos look in the Lab?
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Poor quality oocytes
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A fertilized egg is identified by presence of 2 pronucleus and 2 polar bodies
Development of Embryo
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All couples wishing to start an IVF/ICSI cycle must decide the fate of eggs, which fail to fertilize, sperm and spare embryos remaining after your treatment. If the eggs do not fertilize within 24 hours they will not become embryos and will be destroyed unless you choose to donate them for research. Having decided how many embryos to be replaced, you must decide whether you wish to consider freezing of the spare embryos for later use. In all cases the best embryos will be transferred and the remainder assessed for suitability for freezing, if desired. Any spare embryos will be destroyed in a manner, which is acceptable to you, unless you choose to donate them for research.
Although the research may not be of direct benefit to you, it is aimed at improving our understanding of human development and genetic disease and thereby improving the success of this type of treatment.
You are under no obligation to agree to your spare eggs or embryos being used for research in order to be accepted for treatment.
Gamete intrafallopian transfer (GIFT)
Gamete intrafallopian transfer follows the same procedures as IVF, except that fertilization occurs in the body (in vivo). The eggs and sperm are placed directly in the fallopian tube where fertilization can occur.
Cases in which GIFT may be recommended
- Endometriosis with patent tubes
- Cervical mucus hostility/dysfunction
- Failure of IUI
Advantages of GIFT
- Natural environment for fertilisation
- Less technically demanding
Disadvantages of GIFT
- Fertilisation not confirmed
- Tubes must be unobstructed
- General anaesthesia
ART in male infertility
Some of the ART procedures described as treatment for female infertility are relevant to certain types of male infertility. These include IUI & IVF for mild to moderate factor & ICSI for severe male factor & in patients with antisperm antibodies & failed fertilization with IVF
Intracytoplasmic sperm injection (ICSI)
Intracytoplasmic sperm injection is a micromanipulation technique in which fertilization is brought about by the injection of a single spermatozoon into an unfertilized egg (or oocyte, - see illustration 7). ICSI is performed with eggs obtained after ovulation stimulation as for IVF, and has greatly improved the treatment of male infertility as a result of severe oligozoospermia (abnormally low sperm count). The pregnancy rate with this procedure varies between 25 – 35 %.
Intracytoplasmic sperm injection (ICSI) has revolutionized the treatment of male infertility. Men previously considered untreatable with conditions such as congenital bilateral absence of the vas deferens and very low sperm counts (oligospermia) are now potentially able to initiate a pregnancy with ICSI.
Interest in the initial types of micromanipulation procedures, such as zona drilling and partial zona dissection (PZD), evolved because of the disappointing results of standard IVF for the severe male factor patient. In these procedures, a physical opening is created in the zona pellucida by using chemical "drilling" or by making a microscopic mechanical incision. Subzonal insertion of sperm (SUZI), the microinjection of spermatozoa into the perivitelline space (between the zona pellucida and the plasma membrane), gained popularity for severe male factor infertility because typically only 3 to 4 sperm were inserted per oocyte. The high rate of polyspermy, a lethal condition involving the entrance of more than 1 sperm into the egg and a problem with PZD and SUZI, was finally overcome with ICSI, which requires the injection of only a single sperm per egg. Because of higher clinical pregnancy rates and broader applicability for severe male factor infertility, ICSI has now replaced PZD and SUZI
ICSI requires only one spermatozoon for each egg and because of this, its indications have been expanded to include nearly all men with serious infertility, including many who would previously have been considered hopeless cases. Provided the spermatozoa are viable, even sperm dysfunction may be overcome, since more than 50% of eggs fertilize normally regardless of the sperm quality. Obstructive azoospermia (absence of sperm in the ejaculate) can also be treated by retrieval of spermatozoa directly from the epididymis or testes and even immature spermatozoa have been used to produce embryos.
Schematic Illustration of Intracytoplasmic sperm injection (ICSI)
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Casessin, which ICSI may be recommended
- Severe oligospermia - Very low numbers of motile sperm with normal appearance
- Severe asthenospermia (decreased sperm motility)
- Abnormal sperm morphology (teratospermia)
- Obstructive azoospermia requiring MESA
- Congenital bilateral absence of the vas deferens
- Failed vasectomy reversal
- Acquired epididymal or vasal obstruction
- Abnormal sperm function
- Defective acrosome reaction or capacitation
- • Abnormal sperm penetration - Problems with sperm binding to and penetrating the egg
- Antisperm antibodies (immune or protective proteins which attack and destroy sperm) of sufficient quality to prevent fertilization
- Prior fertilization failure with standard IVF culture and fertilization methods
- Absence of sperm in the seminal fluid
- Day # 2 ICSI after failed IVF ("rescue" ICSI)
Advantages of ICSI
Most effective procedure for male infertility
Overcomes some sperm quality problems
Disadvantages of ICSI
Possibility of transmitting infertility to offspring
Price / costs
"Rescue" ICSI involves microinjection of oocytes that have unexpectedly failed to fertilize after conventional IVF. ICSI can be performed when few or no oocytes are fertilized after one day and is preferable due to the poor results of second-day routine IVF insemination.
After Previously Failed IVF
The failure to fertilize in a previous cycle of IVF is an indication for ICSI because of probable impaired sperm penetrating capabilities. Successful ongoing ICSI pregnancies have been reported in large series of patients who have failed previous IVF or had too few spermatozoa for conventional IVF.
When high quantities of antisperm antibodies are present in the male, treatment with corticosteroid therapy, sperm washing, and routine IVF has been frustrating and often unsuccessful. Consequently, ICSI is now recommended as the primary choice of treatment in this patient population. ICSI appears to bypass the problems of impaired sperm binding and penetration of the zona pellucida, resulting in higher fertilization and pregnancy rates.
Teratospermia (Abnormal Sperm Shape - Morphology)
The poor results with conventional IVF in the presence of teratospermia have been described using the Kruger strict morphology criteria, especially when fewer than 4% normal sperm forms are found. Although the indications for ICSI with teratospermia are not fully defined, ICSI should be the treatment of choice after failed IVF, despite using high sperm concentrations.
Severe Oligoasthenospermia and Testicular Failure
The best results with ICSI fertilization rates are reported using ejaculated sperm, even in the presence of severe defects in sperm density, motility, and/or morphology. While good results are now observed using testicular and epididymal sperm, ejaculated sperm should be used when this option exists. In testicular failure with no sperm in the ejaculate, testicular sperm extraction (TESE) combined with ICSI has resulted in successful ongoing pregnancies.
Obstructive Azoospermia: Congenital Absence of the Vas Deferens, Failed Vasectomy Reversal, and Acquired Epididymal Occlusion
The results of microepididymal sperm aspiration (MESA) combined with IVF and ICSI for obstructive azoospermia are far superior to conventional IVF. ICSI is clearly the treatment choice for men with surgically noncorrectable vasoepididymal lesions. Successful percutaneous epididymal sperm aspiration (PESA) has been described, but the blind and potentially damaging nature of the procedure discourage its routine use.
The cryopreservation of sperm in men undergoing MESA or vasectomy reversal should be strongly considered given the success of using thawed spermatozoa for ICSI. TESE with ICSI has been used for azoospermic men when no sperm can be recovered from the epididymis, most often with complete absence of the epididymis or a massively scarred epididymis.
Abnormal Sperm Function
Because of impaired sperm function and poor fertilization rates after electroejaculation in anejaculatory patients (e.g., spinal cord injury) using intrauterine insemination or standard IVF, ICSI may have a prominent role in this group of patients.
ICSI begins with oocyte retrieval using transvaginal ultrasound-guided puncture at the time of optimal follicular development following appropriate hormonal stimulation. After a brief incubation, mature oocytes are candidates for ICSI. Sperm preparation typically uses a sperm wash, swim-up procedure, or density gradient centrifugation, depending on the source of the specimen and the sperm characteristics. Sperm sources include fresh and frozen routine ejaculates, microepididymal sperm aspirates, and testis biopsy.
Micromanipulation procedures are performed using an inverted phase-contrast microscope at 400X. With the sperm and oocytes in the Petri dish, a single motile sperm with grossly normal morphology is aspirated tail-first into the injection pipette. The micropipette is pushed through the zona pellucida until the ooplasm is entered. The needle is withdrawn after introduction of the spermatozoa into the oocyte.
After 16 to 18 hours of incubation, the oocytes are examined for the presence of normal fertilization. Embryo transfer can be performed from 1 to 3 days after oocyte harvest. Depending on maternal age and the reproductive endocrinologist's preferences, generally 3 to 6 of the morphologically best embryos are transferred to the uterus, while the remaining embryos are frozen.
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Development of Embryo
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Determinants of Success of ART
With even the most severe of male factor sperm defects treatable using ICSI, female factors such as age and oocyte quality are being examined more closely. While the severities of semen abnormalities demonstrate little correlation with ICSI results, egg number and egg quality are now the main determinants of success. Poorer results with ICSI/IVF have been observed in women 40 years of age or older, likely due to poorer oocyte quality and diminished oocyte retrieval after ovarian hyperstimulation. The success also depends on duration ofm infertility, previous pregnancy history & number of previous treatment cycles.
The success rate in ICSI is also greatly influenced by the quality of sperm preparation, whether sperms are obtained from the ejaculated semen sample, epididymis or testis, morphology and by the skill of micromanipulation.
Despite concerns with the possibility of an increased risk of birth defects from ICSI, no convincing data have been demonstrated thus far. Only if the male factor is due to alteration in the gene on “Y” chromosome, this abnormality can be transferred to the male offspring also.
Recent Advances in ART
1. New approaches to ovarain stimulation
- Well controlled production
- Potential for improved batch-to-batch consistency
- Potential for development of compounds with altered half-lives and biopotency
- Absence of biological contamination
- High specific activity and potency
- Despite devoid of LH induces normal follicular development
- Higher receptor binding to granulosa cells and better signal transduction results in higher intrinsic bioactivity
- Lower total dose in shorter treatment period
- More oocytes were retrieved, more embryos obtained, resulting in more pregnancies when the results of cryo-program included
- For prevention of premature LH surge
- Immediately suppress GTs by blocking GnRh receptor restricting treatment only to those days when LH surge likely to occur
- Mechanism of action dependent on equilibrium between endogenous GnRh and dose of applied antagonist
- Lower GT consumption
- Lower risk of OHSS
- Ability to use bolus GnRh agonist to trigger midcycle LH surge
2. Development of more appropriate culture media –
For Blastocyst culture
Development of more appropriate sequential culture media have enabled embryos to be grown for extended periods of time in culture.This helps in choosing the right embryo , towards single embryo transfer in the 21st centaury . This lead to blastocyst culture which has improved implantation & pregnancy rate & reduced the incidence of multiple pregnancies
Human embryos metabolically dynamic with metabolic requirements changing from day to day and stage to stage
Early cleavage embryos require minimal glucose while late blastocyst require plenty of glucose
Pyruvate requirements vice versa
Antioxidant taurine beneficial for blastocyst development while hypoxanthine detrimental
Albumin and not serum essential – precise role not known
3. Microdroplet culture under oil culture system has definitely improved the fertilization rate
Microdroplets of 5 – 50 microlitres under mineral oil equilibrated with CO2
Maintains osmolarity and pH of media both inside incubator when door opened and while screening of embryos at the work station
Prevents fluctuation of temperature
Better cleavage rate with good quality embryos for transfer and cryopreservation
4. In-vitro oocyte maturation
In-vitro oocyte maturation -- primary oocytes recovered from small & growing follicles >/= 3 mm from ovaries of untreated women can be matured in vitro and then fertilized and developed in vitro and then transferred into the uterus
Goal: Immature oocytes matured in-vitro should have competent cytoplasmic & nuclear maturation and consequent embryo formed should have acceptable implantation rate
Limited practice due to scant knowledge of factors controlling developmental competence
Requires mimicking microendocrine environment of developing follicle
OR of –
Oocytes with or without exposure to GTs in vivo
Unstimulated polycystic ovaries
Steps involved in In-vitro oocyte maturation
- Immature oocyte retrival (2-10 mm)
- In vitro maturation
- Sperm preparation
- Insemination or ICSI
- Endometrial preparation with HRT (Estrogens & progesterone)
- Embryo transfer
Future of In-vitro oocyte maturation
Eliminate medication to recruit cohort of follicles for OR
Reduce risk of OHSS
Reduce risk of long-term implications of ovarian carcinoma
Reduce cost of treatment
Assessment of oocyte quality by OR at diagnostic laproscopy
Pregnancy rate 2 % by Cha KY et al 1991
Till date only few pregnancies reported
5. Blastocyst culture
Two major contributory factors for poor take home baby rate
- Reduced viability of replaced embryos
- Asynchrony of stage of replaced embryo and uterine environment (stimulated endometrium)
Blastocyst culture is for improved take home baby rate. But blastocyst culture may reduce the number of embryo transfers as all embryos may not grow to the blastocyst stage & may be arrested at 4 or 6 cell stage, thus resulting in cancellation of the entire cycle.
- Requires sequential media
- Day 5 or 6 transfer
- Blastulation rate 68 – 70 %
- Implantation rate increased – From 19 to 33 %
- Pregnancy rare increased – From 37 to 58 %
- Delivery rate per transfer – 52 % compared to 25% of day 2 or 3 transfer
- With optimal cryopreservation high cumulative take home baby rate with replacement of single blastocyst (zona intact or zona free)
Blastocyst transfer gives opportunity to select better embryos with temporal synchronization of embryo and endometrium at ER
Pregnancy & live birth rate per ovum pick up similar in 2 groups but higher per embryo transfer for blastocyst transfers
6. Assisted Fertilization through Micromanipulation
A) ICSI - Ejaculated sperms, MESA, TESA
Already discussed I male infertility management
B) ICSI – ROSI – Using Immature germ cell - spermatid injection
Spermatid injection or ROSI performed when no sperms seen in testicular tissue with maturation arrest beyond spermatid stage
- Identification of spermatid – semen or TESA
- Preparation of spermatid
- Denuding of oocyte
- Aspiration of spermatid in injection needle
- Injection of spermatid
- Culturing of oocyte and embryo in microdroplets
With ROSI risk of genomic imprinting abnormalities higher besides transmission of infertility gene which is a major concern
C) PGD - Cell biopsy of the embryo to determine genetic status of the embryo. Child born with a genetic disease is a problem for the child itself, parents & society. One could diagnose these defects by CVB at 9 weeks or amniocentesis at 16-18 weeks & terminate pregnancy if abnormal. With this one could not detect abnormalities in fetuses of patients with repeated 1st trimester early abortions . PGD enables us to diagnose genetic disease in human embryo before implantation, thus giving parents a chance to start pregnancy free of inherited disorder
PGD can be done either in Unfertilized egg by removal of 1st polar body or fertilized multi-cellular embryo by removal of 1 or more cells
- Autosomal recessive disorders
- Cystic fibrosis
- Tay Sachs disease
- Sickle cell anaemia
- Autosomal dominant disorders
- Marfans syndrome
- Polyposis coli
- Charcot Marie tooth
- X linked recessive disorders
- Lesch Nyhan Syndrome
- Duchenne Muscular dystrophy
- Aneuploidy or genetic screening in male infertility following ICSI
- Aneuploidy sreening in women with advanced maternal age
- Aneuploidy in translocation carriers
- Single gene defect
1.PCR – Polymerase chain reaction for diagnosing single gene defects and embryo sex determination. It is also used for determining sperm DNA fragmentation which predicts the success of any form of treatment and also helps in selecting the modality of treatment offered.
2.FISH – Fluorescent in situ hybridization for chromosome related aneuploidy and x linked recessive disorders
D) Assisted Hatching – is useful for those viable embryos unable to implant as a result of their inability to break free from surrounding zona pellucida at blastocyst stage.
Inappropriate ovarian environment due to advanced maternal age or other factors that may compromise the follicular environment may in certain cases render the zona pellucida thicker & tougher. But various studies have shown, assisted hatching not to be an effective treatment.
Procedure: Day 3 of OR or D ay 5/6 before ET
Hole made in zona pellucida prior to transfer for embryo to hatch free from zona pellucida
Methods of Hatching
- Chemical – Acid tyrode solution
Assisted hatching does not improve pregnancy rates and therefore not recommended, except in
women >38 yrs, with elevated D3 FSH and repeated IVF failures.
E) Removal of 1 PN from 3 PN embryos
Abnormal fertilization with presence of 3 PN due to polyspermy
- 1 PN removed and embryo cultured further
- Experimental stages
- Trials on
- Results not published
Complications of ART
- Related to stimulation
- Inadequate response
- Excessive response
- Abnormalities in LH surge
- Related to oocyte recovery
- Allergic reaction to drugs
- Related to embryo replacement
- Inability to enter uterine cavity due to acute angulations or presence of ridges in cervical canal
- Traumatic embryo replacement resulting in haemorrhag or endometroma
- Procedure completed under anaesthesia
- Related to luteal phase
- Mainly related to ovarian hyper stimulation syndrome
Are there any long term complications of fertility treatment?
- So far, little data are available as to the possible increased risk ovarian cancer after treatment with fertility drugs. The current opinion among fertility specialists is that these drugs are safe, but should only be administered by specialist in reproductive medicine.
- It has been suggested though not confirmed that stimulation of ovaries can use up all follicles and there by cause a early menopause.
When do you know that you are pregnant?
A biochemical pregnancy can be diagnosed 15 days after IUI or oocyte retrieval by doing the beta hCG levels in the blood. A gestational sac can be seen in the uterine cavity 6 days after the missed period & the fetal pole seen 12 –14 days after the missed periods. The fetal heart can be seen at the same time thus confirming its viability.
The success of any fertility treatment is dependent on important factors such as:
- The age of the woman at the time of treatment (fertility in women starts to decrease at 35 and falls more dramatically after 40);
- The duration of infertility prior to treatment;
- The existence of any infertility problems in the male partner.
- Chances of conceiving through ART have steadily increased over the last few years, with the simplification of treatment procedures, the improvement of drug regimens and routine ultrasound monitoring.
- Stress & unrealistic expectations also affect the success greatly. Unrealistic expectations lack insight & an inflexibility in thinking which results in inability to cope with failures of both i.e. failure to conceive & loss of early or late pregnancy.