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REVIEW ARTICLE
Year : 2009  |  Volume : 53  |  Issue : 4  |  Page : 408-413 Table of Contents     

Anaesthesia for In Vitro Fertilisation


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 Publication3-Mar-2010

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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

How to cite this URL:
Jain D, Kohli A, Gupta L, Bhadoria P, Anand R. Anaesthesia for In Vitro Fertilisation. Indian J Anaesth [serial online] 2009 [cited 2019 Dec 9];53:408-13. Available from: http://www.ijaweb.org/text.asp?2009/53/4/408/60311


   Introduction Top


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% [1] .

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.

  1. Broadly speaking IVF involves the following steps
  2. Ovarian stimulation
  3. Egg collection
  4. Sperm processing & amp;



   Discussion Top


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 [2],[3]

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 [4] . 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 [5],[6],[7],[8] .

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:

  1. Monitored sedation with/without local anaesthesia
  2. General Anaesthesia
  3. 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% [9] .

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 [10]
  • In UK, 84% of the centres now use sedation [11]


Monitored anaesthesiatechnique with remifentanil resulted in a higher pregnancy rate than GA with alfentanil+ prop ofol orisoflurane +propofol for main­ tenance [12] .

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 [13] . Midazolam was found to be safe for sedation in oocvte retrieval [14],[15] .

General Anaesthesia

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 [16] 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

Propofol

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 [17],[18] , a recent study showed that although propofol follicular concentration increases with time, there was no difference in the rates of mature to imma­ture oocytes [19]

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 [19],[20] .

Role of Nitrous - Oxide

Its role still remains controversial.
Gonen etal found out that nitrous oxide has deleterious effect on IVF outcome [21] 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 [22],[23]

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 [14]

Benzodiazepine

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 [24] . Acombination ofmidazolam and fentanylwas found to be safe for oocyte retrieval [5],[25] .

Narcotics

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 [26],[27] . Affentanil follicularfluid level is 10 fold smallerthan the serum concentration at the same point [28] .

Ketamine

Arandomized prospective study; foundthe com­bination of midazo!am and ketamine a good alternative to general anaesthesia [29] .

Drugs to be avoided

Inhalational Agents

Majority of studies have shown detrimental effect of halogenated fluorocarbons with N20 resulting in decreased clevagerates and increased abortions [30] .

Matt etal in 1991 found no significant effect of N20 and isoflurane anaesthesia on human IVF preg­nancy rate [22] .

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 [31],[32],[33],[34], Corson etal have even used paracervical block with bupivacaine forpain relief dur­ing oocyte aspiration [35] . Various conscious sedation regi­mens using midazolam, diazepam, alfentanyl have been used along with paracervical blockto enhance the an­algesia [32] . Electroacupunture has also been used with paracervicalblockto improve the effectiveness of pain relief [36] .

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 [37] . Tsen had compared low dose bupivacaine +fentanyl with lidocaine+fentanylfor oo­cyte retrieval and did not find any combination supe­riorto other [38] .

c. Epidural anaesthesia also forms a viable op­tion but does not demonstrate any advantage over in­ travenous sedation [39] .

2. Bupivacaine compared favorablyto lidocaine in all aspect except takingapproximately 30 min longer to micturition and to discharge [40] .

3. Honnonalresponse to follicular puncture is fully attenuated by regional anaesthesia and partially by tech­nique requiring sedation [41] .

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:

  1. Sympathoinhibitory
  2. Increased beta-endorphin levels
  3. Antidepressant, anxiolytic
  4. Neuroendocrine effect on hypothalamic -pituatry­ovarian axis
  5. Increased uterine blood flow


Electmacupuneture has been used with along with paracervical block for analgesia during oocyte re­trieval [42] . Various conscious sedation regimens have been used alongwith electroacupunctureto enahance analgesia for oocyte retrieval [43],[44],[45] .

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.

 
   References Top

1.Trout SW, VallerandAH, Kemm annE. Conscious sedation for in vitro fertilization used inparacervical block during oocyte retrieval. JAssistReprod Genet 2003; 20: 8-12.  Back to cited text no. 1      
2.Tanbo T, Henriksen T, Magnus O, Abyholm T. Oocyte retrieval in an IVF program . Acorn parison of laparoscopic and vaginal ultrasound guided follicular puncture. Acta Obstet Gynecol Scand 1988; 67:243-246.  Back to cited text no. 2      
3.Ng EH, Chui DK, Tang OS, Ho PC. Para cervical block with and without conscious sedation: a comparison of the pain levels during egg collection and the postop­erative side effects. Fertil Steril 2001; 75:711-717.  Back to cited text no. 3      
4.Stener-Victorin E. The pain-relieving effect of electro­acupuncture and conventional medical analgesic meth­ods during oocyte retrieval: a systemic review of ran­domized controlled trials. Human Reproduction 2005; 20:339-349.  Back to cited text no. 4      
5.Trout Std', Vallenand AH, Kemm ann E. Conscious se­dation for in vitro fertilization. Fertil Steri11998;69:799-808.  Back to cited text no. 5      
6.Ceme A, Bergh C, Borg K, EkI, Gejcrvall AL, Hillensjo T, Olofsson JI, Stener-Victorin E, Wood M, Westlander G. Pre-ovarian block versus paracerv ical block for oocyte retrieval. Human Reproduction 2006; 21:2916-2921.  Back to cited text no. 6      
7.Stener-Victorin E, Waldenstrom U, Wiland M, Nilsson L, Hagglund L, Lundberg T. Electro-acupuncture as peroperative analgesic method and its effects on im­plantation rate and neuropeptide Y concentrations in follicular fluid. Human Reproduction 2003;18:1454-1460.  Back to cited text no. 7      
8.Katzenschlager SMS, Wolfer MM, Langenecker SAK, Sator K, Sator PG Li B, Heinze G, Sator MO. Auricular electro-acupuncture as an additional perioperative an­algesic method during oocyte aspiration in IVF treat­ment. Humanreproduction2006 21:2114-2120.  Back to cited text no. 8      
9.Bokhari A, Poland B. Anesthesia for assisted concep­tion: a survey of UK practice. Eur J Anaesthesiol 1999;16:225-30.  Back to cited text no. 9      
10.Ditkoff B, PlumbJ, SelickA, Saucer M.Anesthesia lnac­tice in the United States common to in vitro fertilization centers. JAssistedRepord Genet 1997:14:145-7.  Back to cited text no. 10      
11.Elkington N, Kehoe J, Acharya U. Recommendations for good practice for sedation in assisted conception. Hum Ferti12003;6:77-80.  Back to cited text no. 11      
12.Wilhelm W, Hamm adehM, White P, et al. General anes­thesia versus monitored anesthesia care with remifentanil for assisted reproductive technologies: ef­fect onpregnancyrate. J C1inAnesth 2002;14:1-5.  Back to cited text no. 12      
13.HadimiogluN,TitzT,DosemeciL,ErmanMComparision of various sedation regimes for traps vaginal oocyte retrieval. Fertil Steril2002;78:648-9  Back to cited text no. 13      
14.Soussis I, Boyd O, Paraschos T, et al. Follicular fluid levels ofmidazolam, fentanyl, and alfentanil duringtrans­vaginal oocyte retrieval. Fertil Steri11995;64:1003-1007.  Back to cited text no. 14      
15.Ben-Shlomo I, Moskovich R, Katz Y, Shaley E. Ivlidazolam/ketamine sedative combination compared with fentanyl/propofol/isoflurane anesthesia for oocyte retrieval. Hum Repord 1999;14:1757-9.  Back to cited text no. 15      
16.Hammadeh ME, Wilhehn W, HuppertA, Rosenbaum P, Schmidt W. Effects of general anesthesia vs sedation on fertilization cleavage and pregnancy rates in an 1W program. ArchGynecol Obstet 1999;263:56-9.  Back to cited text no. 16      
17.Palot Ivi HarikaG, Visseaux H, etal. Use ofnitric oxide in general anaesthesia for oocyte retrieval. Ann Fr Anesth Reanim 1989;8:R147.  Back to cited text no. 17      
18.Dupypere HT, Dhont M, De Sutter P, et al. The influ­ence of propofol on in vito fertilizationin mice Program on the 7 th World conference on IVF and Assisted Proceations; Jun 30-July 3 1991. Paris: World conference on IVF and Assisted Proceations.1991:151.  Back to cited text no. 18      
19.Ben-Shlomo I, MoskovichR, Golan J, et al. The effect of propofol anesthesia on oocyte fertilization and early embryo quality.Hum Repord2000;1 5:21 97-9.  Back to cited text no. 19      
20.Christiaens F, Janssenswillen C, Verborgh C, Moerm an I, DevroeyP, Steirteghem AV Camu F. Propofol concen­trations in follicular fluid during general anaesthesia for transvaginal oocyte retrieval. Human Reproduction 1999;14:345-348.  Back to cited text no. 20      
21.Gonen O, Shulman A, Ghetler Y, et al. The impact of different types of anesthesia on in vitro fertilization­embryo transfer treatment outcom e. J Assist Repord Genet 1995;12:678-82.  Back to cited text no. 21      
22.Matt DW Steingold KA, Dastvan CM, et al. Effects of sera from patients given various anesthetics on pre im­plantationmouse embryo development invitro. JIn Vitro FertEmbryoTransf 1991;8:191-7.  Back to cited text no. 22      
23.Rosen M, Roizen M, Eger E, et al. The effect of nitrous oxide on in vitro fertilization success rate. Anesthesiol­ogy) 987;67:42-4.  Back to cited text no. 23      
24.Chapineau J, Bazin J-E, Terrisse M-P, et al. Assay for midazolam in liquor follicular during invitro fertilization under anaesthesia. ClinPharm 1993;12:770-3  Back to cited text no. 24      
25.Swanson R, Leavitt M. Fertilization and mouse embryo development in the presence of midazolam. Anesth Anaig 1992; 74:549-54  Back to cited text no. 25      
26.Schoeffler PF, Levron JC, Hany L, et al. Follicular con­centration of fentanyl during laparoscopy for oocyte retrieval- correlation with in vitro fertilization results. Anesthesiology 198 8;69:A663.  Back to cited text no. 26      
27.Endler GC, Stout M, Magyar DM, et al. Follicular fluid concentration of thiopentone and thiamylal during laproscopy for o ocyteretrieval. Fertil Steril 198 7;48 :828-33  Back to cited text no. 27      
28.Shapira S, C'hrubasikS,HoffinanA, et al. Use of alfentanil for in vitro fertilization oocyte retrieval. J Clin Anesth 1996; 8:282-5.  Back to cited text no. 28      
29.Naito T, Tam ai S, Fukata J, et al. Comparision of endocri­nological stress response associated with traps vaginal ultrasound-guided oocyte pick up under halothane an­esthesia and neurolept anesthesia. Can J Anesth 1989 36:633-6.  Back to cited text no. 29      
30.Jennings J, Moreland K, Peterson CM. In vitro fertiliza­tion: a review of drug therapy and clinical management. Drugs 1996;52:313-43  Back to cited text no. 30      
31.Wildand M, Evers H, Jacobsson AH, Sandgvist U, Sjoblom P. The concentration of lidocaine in follicular fluid when used for paracervical block in a hum an IVF­ET programme . Human Reproduction 1990 5 :920-23.  Back to cited text no. 31      
32.Ng EHY, Tang OS, Chui DKC, Ho PC. A prospective, randomized, double-blind and placebo - controlled study to assess the efficacy of paracervical block in the pain relief during egg collection in IVF. Hum an Repro­duction 1999;14:2783-87.  Back to cited text no. 32      
33.Ng EHY, Tang OS, Chui DKC, Ho PC. Comparison of two different doses of lidocaine used in paracervical block during oocyte retrieval. J Assist Reprod Genet 2000;15 2148-52.  Back to cited text no. 33      
34.Ng EHY Miao B, Ho PC. Arandomized double- blind study to compare the effectiveness of three different doses of lignocaine used in paracervical block during oocyte retrieval. JAssistReprod Genet 2003;20:8-12.  Back to cited text no. 34      
35.CorsonL, Batzer FR, Gocial B, Ke11yM, Gutmann JN, English 1vIE.Is paracervical block anaesthesia for oo­cyte retrieval effective? Fertil Steril 1994;62:133-6.  Back to cited text no. 35      
36.Stener-VictorinE, Waldenstrom U,NilssonL, Wikland M, Janson PO. A prospective randomized study of electro -acupuncture versus alfentanyl as anesthesia during oocyte aspiration in-vitro fertilization. Human reproduction 1999;14:2480-84.  Back to cited text no. 36      
37.Martin R, Tsen L, Tzeng G, et al. Anesthesia for in vitro fertilization: the addition of fentanyl 1.5% lidocaine. AnesthAnalg 1999;88:523-6.  Back to cited text no. 37      
38.Tsen L, Schultz R, Martin R, et al. Intrathecal low dose bupivacaine versus lidocaine for in vitro fertilization procedures . RegAnesth Pain Med 2000;26:52-6.  Back to cited text no. 38      
39.Botta G D' Angelo A, Giovanni D, et al. Epidural anes­thesia in an in vitro fertilization and embryo transfer program. JAssist Reprod Genet 1995;12:187-90.  Back to cited text no. 39      
40.Endler G, Magyar D, Hayes lvi, Moghissi K. Use of spi­nal anesthesia in laparoscopy for in vitro fertilization. Ferti Steril 1985;43:809-10.  Back to cited text no. 40      
41.Forman RG Fischel SB, Edwards RG, Waiters E. The influence of transient hyperprolactemia on in vito fer­tilization in humans. J Clin Endocrinol Metab 1985;60:517-22.  Back to cited text no. 41      
42.Han JS. Acupuncture: neuropeptide release produced by electric stimulation of different frequencies. Treends Neurosci 2003; 26:17-22.  Back to cited text no. 42      
43.Andersson S, Lundeberg T. Acupuncture from empiri­cism to science: functional background to acupuncture effects in pain and disease. Med Hypotheses 1995;45:271-81.  Back to cited text no. 43      
44.Humaiden P, Stener- Victorin E. Pain relief during oo­cyte retrieval with a short duration electro.acupuncture technique-an alternative to conventional analgesic meth­ods. Hum anReproduction 2004;19:1367-72.  Back to cited text no. 44      
45.Ernest Hung Yu Ng,Oi ,Shan Tang, David Kwan Chi Chue, PakChung Ho. Comparison of two different doses of lignocaine used in paracervical block during oocyte collection in an IVF programme. Hum Reprod 2000;15:2148-51.  Back to cited text no. 45      




 

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