|Year : 2009 | Volume
| Issue : 4 | Page : 408-413
Anaesthesia for In Vitro Fertilisation
Divya Jain1, Amit Kohli2, Lalit Gupta2, Poonam Bhadoria3, Raktima Anand4
1 Assistant Professor, Department of Anaesthesiology and Intensive Care, Maulana Azad Medical College, New Delhi, India
2 Senior Resident, Department of Anaesthesiology and Intensive Care, Maulana Azad Medical College, New Delhi, India
3 Professor, Department of Anaesthesiology and Intensive Care, Maulana Azad Medical College, New Delhi, India
4 Director Professor and Head, Department of Anaesthesiology and Intensive Care, Maulana Azad Medical College, New Delhi, India
|Date of Web Publication||3-Mar-2010|
4-LF, Todarmal Square, Todarmal Lane, BarakhambaRoad(Bengalimarket),NewDelhi 110001
Source of Support: None, Conflict of Interest: None
In vitro fertilization is an upcoming speciality. Anaesthesia during assisted reproductive technique is generally required during oocyte retrieval, which forms one of the fundamental steps during the entire procedure. Till date variety of techniques like conscious sedation, general anaesthesia and regional anaesthesia has been tried with none being superior to the other. However irrespective of the technique the key point of anaesthesia for in vitro fertilization is to provide the anaesthetic exposure for least duration so as to avoid its detrimental effects on the embryo cleavage and fertilization.
Keywords: In vitro fertillization, Monitored anaesthesia, General anaesthesia, Regional anaesthesia
|How to cite this article:|
Jain D, Kohli A, Gupta L, Bhadoria P, Anand R. Anaesthesia for In Vitro Fertilisation. Indian J Anaesth 2009;53:408-13
| Introduction|| |
In-vitro fertilization(IVF) started 30 years back when Lesley and John Brown, a young couple from Bristol were unable to conceive for 9 years. Lesley had blocked Fallopian tubes. On 10 th Nov 1977, Lesley underwentthe very experimental in-vitro fertilization by Dr: Patrick Steptor. Finally, on 25 th July 1978 LOUISE JOY BROWN, the 1 st successful test tube baby was born. S incethen there has been continuous refinement in the fertility drugprotocols andthe techniquesto retrieve eggs. As a result, IVF success rates began to climb slowly reaching 25-30%  .
What is In-Vitro Fertilization?
In-Vitro Fertilization is abroad term forthetechnique ofultrasound directed Oocyte retrieval(UDOR) or Trans Vaginal Follicle Aspiration(TVFA) and fertilization in the laboratory with transfer of embryos back into the uterus.
- Broadly speaking IVF involves the following steps
- Ovarian stimulation
- Egg collection
- Sperm processing & amp;
| Discussion|| |
Role of Anaesthesiologist
1980's witnessed a drastic change from the use of laparos cope to vaginal ultrasound probe for egg retrieval. Although this technique of using Vaginal ultrasoundprnbe is less invasive and associatedwith higher pregnancy rates, it forms one of the most stressful and painfulcomponents of the entire assisted reproductive treatment ,
Pain during oocyte retrieval is caused by the puncture of the vaginal skin and ovarian capsule by the aspimtingneedle as well as manipulation within the ovary during the entire procedure  . Here it becomes customary forthe anaesthetist to provide adequate pain relief to immobilise the patient and eliminate the danger of piercing any vessel during the process of oocyte retrieval. The idealpain relief during oocyte retrieval should be effective and safe, easyto administer and monitor, short acting and readily reversible with a few side effects ,,, .
Coexisting illness Patients presenting in the IVF clinic needs to be investigated for any co morbid illnesses. In Indiatuberculosis is the most important cause of infertility; so we need to know the drug interactions of antitubercular drugs with the anaesthetic agents. These patients are generally kept on aspirin or heparin so as to prevent the hypercoaguable state occurring as a result of gonad otrophic injections. Aspirin should ideally be stopped 3 days prior to egg retrieval procedure. In case our patient is on heparin, we needto know the Activated prothromb in time.
Thyroid can also be acause of unfertility so it becomes mandatory to assess the thyroid function tests and take appropriate anaesthetic precautions.
Some of the patients might be receivingtreatment forpsychomotor disorders like depression and are on anti depression drugs like Selective serotonin reuptake inhibitors(SSRI), tricyclins or drugs like tragadone, bupropion. It is therefore importantto adjustthe dosages of anaesthetic agents especially narcotics accordingly.
Anxiety- Another major challenge for the anaesthetistis to allay the anxiety .The patients presenting in the IVF clinic are under high degree of social and psychological stress. Majority of them are in late thirties, and the immense family pressure makes them more susceptible to psychomotorillness like depression and psychosis. Moreoverthis problem is further aggravated by the hormonal manipulation occuring duringin vitro fertilization.
Thus it becomes important to provide them with a comfortable environment so as to extract complete medical and pharmacological history. Nowadays many upcoming IVF centres have a provision for isolated rooms for the pre-anaesthetic checkups. One must remember that proper preoperative counseling is very important in allaying anxiety in such patients.
Types of Anaesthesia
Presently anaesthesia for assisted reproductive tecnique is emerging as a speciality in itself. Patients presenting for IVF can have varied causes for infertility like pelvic inflammatory disease due to tuberculosis, chlamydial infection, history of previous pelvic surgery, tubalblockage or end ometrio sis. Therefore the patients undergo ing this treatment are thoroughly evaluated for the cause of infertility and appropriate treatment instituted. Athorough pre anaesthetic evaluation is required to identify any comorbid illness.
There are many options available to the anaesthesiologist:
- Monitored sedation with/without local anaesthesia
- General Anaesthesia
- Regional Anaesthesia
A survey conducted by Bokhari et al in U.K showed the use of sedation in 46% of the centres, general anaesthesia in 28%, regional anaesthesia with sedation in 12% while a cock tailregime was followed by the rest 14%  .
Monitored anaesthesia care
Monitored anaesthesia is relatively easy to deliver, drugs are well tolerated and best suited in day
care settings. However, it has its own risks of cardiac, respiratory and anaphylactic complications.
- In USA, 95% of the programs use conscious sedation as a part of monitored anaesthesia care 
- In UK, 84% of the centres now use sedation 
Monitored anaesthesiatechnique with remifentanil resulted in a higher pregnancy rate than GA with alfentanil+ prop ofol orisoflurane +propofol for main tenance  .
Hadimioglo etal had studied various combination of sedation regimens for oocyte retrieval.and found no significant difference between propofol +fentanyl, midazolam+fentanyl and propofo l+fentanyl in the recovery characteristics  . Midazolam was found to be safe for sedation in oocvte retrieval , .
Invariably allanaesthetic agents being used in general anaesthesia have been detected in follicular fluid, raising concerns regarding their use. However, with recent studies documentingthe safe use of the agents, balanced anaesthesia with N 2 O and opioids can be an option for anaesthesiologists. Hammadeh etal in 1999, showed ahigher retrieval of oocytes with remifentanil +propofol or isoflurane based general anaesthesia than with sedation with midazolam, diazepam or propofol  This could be attributed to the increased comfort level of both the gynaecologist and the patient. With a relaxed utems, it becomes easierfor the gynaecologist to aspirate eventhe small ovarian follicles, unlike sedation where a contracted myometrium fibrils pose a hinderence for oocyte retrieval. The key is to aim for a pharmacological exposure of shortest duration.
Use of Anaesthetic Drug
While selecting adesired agentour main concerns are:
- Whether the substance enters the follicular fluid?
- What are its toxic effects on the fertilization and clevage and pregnancy rates?
Drugs commonly used
Widely being used in assisted reproduction and its effects on the fertilization, embryo clevage and pregnancy rates has been extensively studied. Propofol has added advantages of antiemetic property along with faster recovery.
Though earlier studies had documented adverse effects of increased exposure to propofol on clevage of oocytes , , a recent study showed that although propofol follicular concentration increases with time, there was no difference in the rates of mature to immature oocytes 
In addition, there was no significant difference found in fertilization rate, clevage and embryo cell number, implantation rate as compared to thiopentone.Except a trend towards low fertilization rate with longer exposure to anaesthetic drug , .
Role of Nitrous - Oxide
Its role still remains controversial. Gonen etal found out that nitrous oxide has deleterious effect on IVF outcome  N 2 0 inactivates methionine synthetase thereby decreasing the amount ofthymidine available for DNA synthesis in dividing cells. However, as the inactivation ofmethionine proceeds slowly in the human liver, the effect of N 2 0 is minimal. Furthermore, the low solubility of N 2 O exposes the oocytes to this gas for a brief duration. Rosen etal in 1987 found no signficant difference between the fertilization or pregnancy rates when comparing isoflurane with 0 2 which was further confirmed by Matt et al ,
While, Hadimioglu N et al in 2002 showed nitrous oxide actually increase the rate of IVF by reducingthe concentration ofotherpotentially toxic and less diffusible anaesthetic drugs 
Midazolam is the most commonly used benzodiazepine. Although minimal amount ofthis benzodiazipine are found in follicular fluid, no detrimental effects have been proven so far  . Acombination ofmidazolam and fentanylwas found to be safe for oocyte retrieval , .
In recent years, various opioids have been used as apart of regime in conscious sedation and monitored care for anesthesia in assisted reproductive technique.
Fentanyl or alfentanil were found to b e favourable agents when used in combination with prop ofol by Hadimioglu etal in 2002. Fentanyl has minimal penetration into follicular fluid , . Affentanil follicularfluid level is 10 fold smallerthan the serum concentration at the same point  .
Arandomized prospective study; foundthe combination of midazo!am and ketamine a good alternative to general anaesthesia  .
Drugs to be avoided
Majority of studies have shown detrimental effect of halogenated fluorocarbons with N20 resulting in decreased clevagerates and increased abortions  .
Matt etal in 1991 found no significant effect of N20 and isoflurane anaesthesia on human IVF pregnancy rate  .
Use of Regional Anaesthesia
1. It constitutes either central neuraxial blockade of the peripheral nueral block.
a. Para cervical block with different doses of lidocaine with sedation has been used by anaesthetist for egg retrieval ,,,, Corson etal have even used paracervical block with bupivacaine forpain relief during oocyte aspiration  . Various conscious sedation regimens using midazolam, diazepam, alfentanyl have been used along with paracervical blockto enhance the analgesia  . Electroacupunture has also been used with paracervicalblockto improve the effectiveness of pain relief  .
b. Spinal anaesthesiais also an effective method. Martin et al in 1998 had used low dose hyperbaric 1.5% lidocaine (45mg) spinal with low dose fentanyl l0mcg for egg retrieval  . Tsen had compared low dose bupivacaine +fentanyl with lidocaine+fentanylfor oocyte retrieval and did not find any combination superiorto other  .
c. Epidural anaesthesia also forms a viable option but does not demonstrate any advantage over in travenous sedation  .
2. Bupivacaine compared favorablyto lidocaine in all aspect except takingapproximately 30 min longer to micturition and to discharge  .
3. Honnonalresponse to follicular puncture is fully attenuated by regional anaesthesia and partially by technique requiring sedation  .
Alternative Therapy : Acupunture
it is a traditional Chinese medicine, nontoxic, relatively affordable,therapy with po ssih le indications as an adjunct in assited reproduction with the following beneficial effects:
- Increased beta-endorphin levels
- Antidepressant, anxiolytic
- Neuroendocrine effect on hypothalamic -pituatryovarian axis
- Increased uterine blood flow
Electmacupuneture has been used with along with paracervical block for analgesia during oocyte retrieval  . Various conscious sedation regimens have been used alongwith electroacupunctureto enahance analgesia for oocyte retrieval ,, .
The technique employed in aspiration of the oocyte and laborotry manipulations have all been modified and updated. Which is better, sedation or general anaesthesia is more of a personal preference. But the anaesthetic which is imp ortantto the comfort level both for the patient and the gynaecologist to maximize the harvesting of oocytes plays an importantrole in the succes slid outcome.
How Safe are Anaesthetic Agents? With the coming up of large prospective trials documenting safe use of drugs like propofol, opioid, the newer anaesthetics have lost theirinhibitions regardingthe use of these agents, thereby wideningthe scope of more rationale anaesthesia in IVF and extending our services to this developing sub-speciality.
The key to anaesthesia in IVF is to aim for pharmacological exposure of shortest duration with minimalp enetration to follicular fluid.
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