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 Table of Contents  
REVIEW ARTICLE
Year : 2015  |  Volume : 5  |  Issue : 2  |  Page : 62-72

Anesthesia for in vitro fertilization


Department of Anesthesiology, AIIMS, New Delhi, India

Date of Web Publication11-Sep-2015

Correspondence Address:
Prof. Anjan Trikha
Room No. 5011, Main AIIMS Building, AIIMS Campusansari Nagar, New Delhi - 110 049
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2249-4472.165132

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  Abstract 

In vitro fertilization (IVF) is one of the most recent advances in the treatment of infertility. The availability and utilization of this technology are increasing by the hour. IVF procedures are usually performed on an outpatient basis under day care surgery units. Various anesthetic modalities and analgesic regimens have been tested in different studies, but no definite conclusion so far been made regarding the preferred technique for anesthesia and pain relief for these procedures. Many anesthetic drugs have been detected in the oocyte follicular fluid and may potentially interfere with oocyte fertilization and implantation. The ideal anesthetic technique for IVF should provide good surgical anesthesia with minimal side effects, a short recovery time, high rate of successful pregnancy, and shortest required duration of exposure. The preferred method of anesthesia and analgesia should be individualized as at present there are no perfect answers.

Keywords: analgesia, in vitro fertilization, oocyte retrieval, sedation


How to cite this article:
Sharma A, Borle A, Trikha A. Anesthesia for in vitro fertilization. J Obstet Anaesth Crit Care 2015;5:62-72

How to cite this URL:
Sharma A, Borle A, Trikha A. Anesthesia for in vitro fertilization. J Obstet Anaesth Crit Care [serial online] 2015 [cited 2019 Oct 14];5:62-72. Available from: http://www.joacc.com/text.asp?2015/5/2/62/165132


  Introduction Top


Advances in medicine have greatly decreased maternal morbidity and mortality. However, this has given the gynecologist a new challenge of dealing with infertility. The most recent and advanced answer to this problem is in vitro fertilization (IVF). [1],[2] Started first in the late 1970s, IVF is now a reasonable answer to infertility due to both maternal and paternal disorders. [3] As always a new surgical technique is another new challenge to the enthusiastic anesthetist. Anesthesia may be required in various aspects of the patient's treatment, which demands judicious perioperative management.

IVF techniques include:

  1. Ovarian stimulation and monitoring.
  2. Ultrasound-directed oocyte retrieval or transvaginal follicle aspiration.
  3. Fertilization in the laboratory and transfer of embryos back into the uterus. [4]


General considerations

Coexisting illness

Patients may be suffering from any medical/surgical disorders. [5],[6],[7],[8],[9] Special emphasis should be made on known/anticipated cause of the infection, that is, tuberculosis [10] and thyroid disorders. [11]

Current medications

Patients may be on anticoagulants, [12] thyroid medications, antidepressants/anxiolytics, [13] analgesics or antitubercular drugs.

Special considerations

Morbid obesity, severe renal/cardiac/pulmonary disease. In cancer patients, oocyte retrieval usually being performed prior to chemo/radiotherapy. [14]

Anesthetic considerations

Oocyte retrieval was previously done laparoscopically but is now being done less invasively through the vagina. [15],[16] This process is very stressful and painful. [17] Previously, it has been reported that due to stress there is 50 fold transient increase in serum prolactin levels during oocyte retrieval under general anesthesia (GA) which may affect IVF outcome. [18] There may be need of repeated exposure of anesthesia for IVF till success is achieved which makes patient anxious.

Adequate pain relief is required for immobilization and eliminates the danger of piercing any vessel and for patient comfort.

Nowadays, the IVF procedures are performed as "day care" cases and the principle of "ambulatory anesthesia" is used in these patients. Anesthetic techniques, pneumoperitoneum (if laparoscopy is required) and pharmacological agents used for IVF are the factors to be taken under considerations. These procedures should not interfere with oocyte fertilization or early embryo development and implantation.

Effect of anesthetic agents on in vitro fertilization techniques

Anesthetic agents have been found in the follicular fluid, and these drugs may have adverse effects on oocyte fertilization and embryonic development. Prolonged period of exposure with GA can lead to lower pregnancy and delivery rates. [18] Pneumoperitoneum with carbon dioxide exposure during laparoscopy may have detrimental effects on oocyte quality and in combination with GA with nitrous oxide (N 2 O) appear to influence fertilization and cleavage in vitro. [19] But, Rosen et al. did not find the deleterious effect of N 2 O on the rates of fertilization or pregnancy when used during an isoflurane-based general anesthetic technique. [20] Short-acting opioids, principally fentanyl and remifentanil, do not alter IVF success rates. [21]

Pharmacological exposure to the anesthetic agents should be for the least possible duration with minimal penetration to follicular fluid. Assessment of specific anesthetic drugs must be interpreted with the method of administration, dose of anesthetic agents, combination with other drugs, timing of administration, and duration of exposure. For example, local anesthetic agents yield dissimilar pharmacokinetic profiles when administered via paracervical, epidural, and intrathecal techniques. Anesthetic agents may also affect unfertilized oocytes and fertilized embryos differently; thus, studies of anesthetic agents used for a (gamete in vitro fertilization-prefertilization) procedure should not be directly compared with studies of agents used for a (zygote in vitro fertilization-postfertilization) procedure. Finally, significantly higher free concentrations of certain agents (e.g., bupivacaine) exist during IVF stimulation because of a decrease in plasma protein binding capacity. [22]

Pain during in vitro fertilization procedures

The pain expressed during aspiration of oocytes is identical to intensive menstrual pain and produced by the needle inserted through the vaginal wall and by mechanical stimulation of the ovary. [17] The number of follicles and duration of the oocyte retrieval procedure may affect the pain intensity. Single follicle aspiration would take lesser time and cause less pain as compared to multiple follicle aspirations. [23] A favorable analgesic regimen for oocyte retrieval must have no toxic effects on the oocytes with rapid onset, rapid recovery, ease of administration, and monitoring. Most frequently opioids and benzodiazepines have been used for pain relief during IVF procedures. Although many of these agents have been found in the follicular fluid, there is a lack of clear evidence to reveal adverse effects on oocytes.

In vitro fertilization anesthesia techniques

Oocyte retrieval for IVF is usually performed transvaginally under ultrasound guidance which is a relatively brief (20 ± 30 min) outpatient procedure. It necessitates a short-acting anesthetic approach with minimal side effects. The various anesthetic modalities used for transvaginal oocyte retrieval include monitored anesthesia care, conscious sedation, GA, regional anesthesia, local injection as a paracervical block (PCB), epidural block, subarachnoid block, total intravenous anesthesia (TIVA), patient-controlled analgesia (PCA), and acupuncture. A survey conducted by Bokhari and Pollard [24] in UK showed the use of sedation in 46% of the centers, GA in 28%, regional anesthesia with sedation in 12% while a cocktail regime was followed by the rest 14%.

Monitored anesthesia care and conscious sedation

Monitored anesthesia care (MAC) is relatively easy to deliver; drugs are well-tolerated and best suited in day care settings. It avoids the potentially harmful effects of anesthetic drugs on oocytes. Different methods of conscious sedation and analgesia have been used for oocytes recovery for IVF techniques. Drugs used for these procedures are selected by the quality of sedation and analgesia and their deleterious effects on reproductive outcomes. According to updated cochrane review conducted in 2013, the various approaches for MAC and conscious sedation used for IVF appeared to be acceptable and were associated with a high degree of satisfaction in women and it was found that simultaneous use of more than one method of sedation and analgesia resulted in better pain relief than one modality alone. [17] The optimal method should be individualized based on the preferences of both the women and the clinicians and resource availability. The various studies [25],[26],[27],[28],[29],[30],[31] in which MAC or conscious sedation used for analgesia for IVF are summarized in [Table 1].
Table 1: MAC, conscious sedation, and IVF outcome


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General anesthesia

Most of the anesthetic agents being used in GA have been found in the follicular fluid. However, in a few studies, it was observed that it can be a safer option for anesthesiologists. As the uterus becomes more relaxed under GA, it is easier for the clinician to aspirate a large number of ovarian follicles, unlike sedation where a contracted myometrium may interfere with oocyte retrieval. The duration of GA should be kept minimum to avoid detrimental effects of these drugs on oocytes. The various studies [32],[33],[34] in which GA used for analgesia for IVF are summarized in [Table 2].
Table 2: GA and IVF outcome


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Paracervical and preovarian block

In PCB, a local anesthetic is injected into 2-6 sites at a depth of 3-7 mm alongside the vaginal portion of the cervix in the vaginal fornices. In comparatively newer technique, preovarian block (POB), the local anesthetic is infiltrated in the vaginal wall under ultrasound guidance between the vaginal wall and peritoneal surface near the ovary. [35] The various studies [36],[37],[38],[39],[40] in which paracervical or POB used for analgesia for IVF are summarized in [Table 3].
Table 3: Paracervical, POB, and IVF outcome


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Spinal anesthesia

Spinal anesthesia is also an efficient method for oocyte retrieval. The various studies [41],[42],[43],[44],[45],[46],[47] in which spinal anesthesia used for IVF are summarized in [Table 4].
Table 4: Spinal anesthesia and IVF outcome


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Epidural anesthesia

Epidural anesthesia is another mode of analgesia for IVF, and it can be a viable option in some conditions. The various studies [48],[49] in which epidural anesthesia used for IVF are summarized in [Table 5].
Table 5: Epidural anesthesia and IVF outcome


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Total intravenous anesthesia

Raftery and Sherry [50] in their study on 80 women found that TIVA with propofol and alfentanil is superior to inhalational anesthesia with N 2 O and enflurane in view of less nausea and vomiting (64% in inhalational group and 39% in TIVA group), less requirement for anti-emetic medication (62% in inhalational group and 32% TIVA group), and a lower probability of unplanned admission to hospital (21% in inhalational group and 5% in TIVA group) after day-care IVF procedures.

Patient controlled analgesia (PCA)

It is an alternative technique of analgesia with higher levels of patient satisfaction by allowing women to control over their drug administration. Bhattacharya et al. [51] in a prospective randomized study compared the effect of fentanyl administered either through a PCA pump (10 μg fentanyl bolus with 1 min lockout interval) or by a physician. The mean pain score in the PCA group was 38.5 (19.8) while in the other group, it was 46.1 (21.3) (P = 0.1). In the PCA group, 64% of women felt very satisfied with their analgesia as compared with 57% in the non-PCA group (P = 0.6). They concluded that although intraoperative PCA with fentanyl is an effective alternative to physician-administered techniques in terms of patient comfort and satisfaction.

Acupunture

It is a conventional therapy which activates the endogenous opioid system by increasing beta-endorphin levels. [52] It has the additional benefit of providing antidepressant, anxiolytic, and sympathoinhibitory actions. It has been used along with various conscious sedation regimens and paracervical block to enhance analgesia during IVF procedures. Humaidan and Stener-Victorin [53] in a prospective randomized study in 200 women investigated the role of electroacupuncture as an alternative to the conventional analgesic method (benzodiazepine premedication and alfentanil 0.25 mg boluses). They found that the procedure was well-tolerated in both the groups, however, higher pain scores were observed in electroacupuncture group. Gejervall et al. in their randomized study on 160 females found that electroacupuncture cannot be generally recommended as a pain relieving method of oocyte aspiration but might be an alternative for women desiring a nonpharmacological method. In a similar study, Stener-Victorin et al. [54] concluded that analgesic effects produced by electroacupuncture are as good as those produced by conventional analgesics, and the use of opioid analgesics with electroacupuncture is lower than when conventional analgesics alone are used.

Anesthetic agents and in vitro fertilization

Local anesthetic agents

The various local anesthetic drugs and their effects [54],[55] on IVF outcomes are summarized in [Table 6].
Table 6: Local anesthetic agents and IVF outcome


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Opioids


Various opioids (fentanyl, alfentanil, remifentanil, and pentazocine) have been used for analgesia for IVF procedures. Their effects [56],[57],[58],[59],[60],[61],[62],[63],[64],[65],[66] on IVF outcomes are summarized in [Table 7].
Table 7: Opioids and IVF outcome


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Benzodiazepine

Midazolam is the most commonly used benzodiazepine for IVF procedures. Although a minimal amount of this benzodiazepine is found in the follicular fluid, no deleterious effects have been demonstrated. The benzodiazepines and their effects [67],[68] on IVF outcomes are summarized in [Table 8].
Table 8: Benzodiazepines and IVF outcome


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Ketamine

The effect of ketamine [69] on IVF outcomes is summarized in [Table 9].
Table 9: Ketamine and IVF outcome


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Propofol and thiopental

Propofol and thiopentone are being used extensively in IVF, and their effects on the fertilization, embryo clevage, and pregnancy rates have been investigated in various studies [70],[71],[72],[73],[74],[75],[76],[77] [Table 10]. Propofol is suitable for day care IVF procedures with added advantages of the antiemetic property along with faster recovery.
Table 10: Propofol and thiopental


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Etomidate

Heytens et al. [79] in a prospective comparative study in 18 patients found that etomidate could also interfere with the endocrine function of the ovary by observing a sharp decrease in the plasma concentration of 17 beta-oestradiol, progesterone, 17-hydroxyprogesterone -progesterone, and testosterone within 10 min after induction of anesthesia with etomidate (0.25 mg/kg) followed by a gradual return to the baseline levels thereafter.

Nitrous oxide

Gonen et al. [80] in their retrospective analysis of three groups sedation combined with local anesthesia, epidural block, and GA with N 2 O found that N 2 O had a deleterious effect on IVF outcome. Significantly lower clinical pregnancy rates were found in N 2 O group (14.5%) compared with epidural group (23.7%; P = 0.018) or sedation group (25.8%; P = 0.0074). N 2 O deactivates methionine synthetase thereby reducing the amount of thymidine available for DNA synthesis in dividing cells. However, this effect is minimal as the inactivation of methionine proceeds slowly in the human liver. Moreover, the low solubility of N 2 O exposes the oocytes to this gas for a short duration. In contrary to this, Hadimioglu et al. [25] demonstrated that N 2 O increase the success rate of IVF by lowering the concentration of other potentially toxic and less diffusible anesthetic drugs. Thus, the effect of N 2 O on IVF outcome still remains questionable.

Volatile halogenated agents

Most of the studies have demonstrated the deleterious effect of halogenated fluorocarbons on IVF outcomes. Matt et al. [81] observed insignificant effect of N 2 O and isoflurane anesthesia on human IVF pregnancy rate. The effects of various volatile agents [81],[82],[83],[84],[85],[86],[87] on IVF outcome are summarized in [Table 11].
Table 11: Volatile halogenated agents


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Postoperative nausea and vomiting and antiemetic agents

Postoperative nausea and vomiting (PONV) is a common problem after IVF procedures under anesthesia, [88],[89] and its frequency is related to peak plasma level of estradiol and previous history of PONV [Table 12]. Higher incidence of PONV was found following inhalational anesthesia for IVF procedures as compared to TIVA.
Table 12: Antiemetic agents, PONV and IVF outcome


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Bromocriptine

Sopelak et al. [91] in their study on 32 patients observed that bromocriptine, a potent dopamine agonist, given before anesthesia can suppress transient, anesthesia-induced hyperprolactinemia, and had have a positive influence on embryonic development.

Nonsteroidal anti-inflammatory drugs

Mialon et al. [92] in a retrospective study compared two analgesic protocols: Paracetamol/alprazolam and nefopam/ketoprofen on IVF outcomes. They found that both groups had similar IVF outcomes and nefopam/ketoprofen protocol enhanced patient comfort without jeopardizing the IVF success rates.


  Conclusion Top


The role of the anesthetist in IVF is to provide adequate comfort and pain relief to the patients during oocytes retrieval and embryo transfer procedures. The modality of the providing the same should depend on the patient cooperation. If the patient is comfortable, conscious sedation is a good option. However, in some cases, regional or GA may be requested. Different studies have explored the effect of anesthesia on IVF outcome but have yielded contradictory findings. These differences may be attributed in relation to differences in the study design and randomization, the anesthetic drugs used, or the anesthetic technique performed. Always pay attention to the comorbidities including those contributing to infertility and the drugs that the patient is taking. Furthermore, the anesthesia should be used for the shortest duration required.

 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12]


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