Pregnancy and Obstetric Complications

Pneumoperitoneum

When faced with providing anesthesia for the pregnant patient undergoing laparoscopic surgery, the anesthesiologist must focus not only on maternal/fetal issues and prevention of preterm labor, but also on patient positioning during surgery and the physiologic and mechanical effects of the carbon dioxide (CO ₂ ) pneumoperitoneum. During laparoscopy, pneumoperitoneum can cause cardiovascular and respiratory alterations in nonpregnant patients, which become accentuated in the parturient. Adding pneumoperitoneum to an enlarged uterus further limits diaphragm expansion and is associated with an increase in peak airway pressure, decrease in FRC, increased ventilation/perfusion (V/Q) mismatching, increased alveolar-arterial O ₂ gradient, decreased thoracic cavity compliance, and increased pleural pressure. Pneumoperitoneum and Trendelenburg positioning moves the carina cephalad, which can convert a low-lying tracheal tube to an endobronchial position. The Trendelenburg position increases intrathoracic pressure and accentuates all the respiratory-related physiologic changes.

The combination of pregnancy and CO ₂ pneumoperitoneum predisposes the parturient to hypercapnia and hypoxemia. Insufflation of CO ₂ results in CO ₂ absorption across the peritoneum and into the maternal bloodstream. Elimination depends on an increase in minute ventilation; however, mechanical hyperventilation can reduce uteroplacental perfusion, probably because of decreased venous return. Although end-tidal CO ₂ concentration (eT co ₂ , P etco ₂ ) correlates well with arterial CO ₂ tension (Pa co ₂ ) in healthy patients, these are poor guides to Pa co ₂ in sicker patients. Any increase in maternal Pa co ₂ or decrease in Pa o ₂ can affect fetal well-being. The cardiovascular changes associated with CO ₂ insufflation include reduction in cardiac index and venous return, which can be exacerbated by reverse Trendelenburg positioning. The observed increase in intracardiac filling pressures is probably secondary to an increase in intrathoracic pressure. The combination of reverse Trendelenburg position, general anesthesia, and peritoneal insufflation can decrease the cardiac index (CI) by as much as 50%.

The hemodynamic effects of aortocaval compression by the gravid uterus could further accentuate the hemodynamic effects of pneumoperitoneum and reverse Trendelenburg positioning, resulting in significant hypotension. Steinbrook and Bhavani-Shankar studied the cardiac output changes in four pregnant patients (17-24 weeks' gestation) undergoing laparoscopic surgery using thoracic bioimpedance cardiography. IV ephedrine (10 mg) was given if SBP decreased by more than 20% with respect to baseline. The authors noted a 27% decrease in CI after 5 minutes of CO ₂ insufflation. CI remained 21% below baseline after 15 minutes of insufflation. The authors' aggressive management of blood pressure during anesthesia (treating any decrease in BP approaching 20% of baseline measurements with IV ephedrine to minimize decreases in uterine blood flow) may have resulted in the somewhat smaller CI reduction during CO ₂ insufflation in their pregnant patients (27%) compared with 30% to 50% in nonpregnant subjects in most studies. Mean arterial pressure (MAP) and systemic vascular resistance (SVR) increased in these study subjects during CO ₂ insufflation, which is similar to that generally observed in nonpregnant subjects during laparoscopic surgery.

Monitoring

With the large number of physiologic changes associated with pregnancy, as well as the cardiovascular and pulmonary changes induced by laparoscopic surgery, optimal perioperative monitoring is unclear. The main debate is whether perioperative monitoring of arterial blood gases (ABGs) and fetal and uterine activity is necessary in parturients undergoing laparoscopic surgery. The Society of American Gastrointestinal Endoscopic Surgeons (SAGES) published guidelines for laparoscopic surgery during pregnancy that include perioperative monitoring of ABGs, as well as perioperative fetal and uterine monitoring, as echoed by other authorities. Amos et al. reported four fetal deaths in seven pregnant women who underwent laparoscopic cholecystectomy or appendectomy. During the same period, no fetal deaths occurred in patients who underwent pelvic surgeries by laparotomy. Even though no ABG data were collected, fetal demise could have resulted from prolonged respiratory acidosis, despite maintaining ET co ₂ in the physiologic range (low to mid-30s mm Hg). These concerns stem from previous studies indicating that elevation in maternal Pa co ₂ could impair fetal CO ₂ excretion across the placenta and could exacerbate fetal acidosis. Other risk factors were present for fetal loss in this series, however, including perforated appendix and pancreatitis.

Steinbrook et al. reported a case series of 10 pregnant women, gestational age 9 to 30 weeks, undergoing laparoscopic cholecystectomy; ABGs or perioperative fetal and uterine activity were not monitored. The patients underwent general anesthesia with controlled ventilation, with ET co ₂ maintained at 32 to 36 mm Hg. Fetal heart rate (FHR) and uterine activity were assessed preoperatively and immediately postoperatively. All patients had an uneventful recovery and did not need postoperative tocolysis, and no adverse maternal or fetal outcomes were noted. Seven patients were followed to delivery and had normal infants. The authors concluded that standard monitors recommended by the American Society of Anesthesiologists (ASA) are sufficient for the safety and well-being of the parturient and the fetus.

Based on a series of 45 laparoscopic cholecystectomies and 22 laparoscopic appendectomies performed during all three trimesters, Affleck et al. supported the use of noninvasive monitors and maintenance of the ET co ₂ within the physiologic range. They also recommended preoperative and postoperative FHR and uterine activity monitoring and no prophylactic tocolysis. No fetal loss or uterine injuries or spontaneous abortions occurred. There was no significant difference in preterm delivery rate, Apgar scores, or birth weights between the open and laparoscopic surgery groups. As in previous reports, the operative groups (both open and laparoscopic appendectomies and cholecystectomies) had a slightly higher rate of preterm labor compared with the general population. Furthermore, multiple case reports have reported successful outcomes with noninvasive monitoring.

Bhavani-Shankar et al. prospectively evaluated the Pa co ₂ -ET co ₂ difference in eight parturients undergoing laparoscopic cholecystectomy with CO ₂ pneumoperitoneum. The intra-abdominal pressures were maintained at about 15 mm Hg. These women underwent surgery with general anesthesia during the second and third trimester. After adjusting minute ventilation to maintain the ET co ₂ at 32 mm Hg, ABGs (alpha-stat method) were measured at fixed surgical phases: before insufflation, during insufflation, after insufflation, and after completion of surgery. The authors found no significant differences in either mean Pa co ₂ -ET co ₂ gradient or Pa co ₂ and pH during the various phases of laparoscopy. During the surgical phase the maximal Pa co ₂ -ET co ₂ difference detected was 3.1 mm Hg (range, 1.1-3.1). It appears that ET co ₂ correlates well with arterial CO ₂ , and adjusting ventilation to maintain ET co ₂ also maintains optimal maternal Pa co ₂ . These results do not support the need for ABG monitoring during laparoscopy in pregnant patients.

Laparoscopic procedures have been performed safely during all trimesters of pregnancy. However, some authors advocate reserving semielective, nonobstetric surgery during pregnancy only during the second trimester. During this period, organogenesis is complete, and spontaneous abortions are less common than in the first trimester. Furthermore, procedures during the third trimester have been associated with more preterm labor and potential difficulty in visualization with an enlarged uterus.

Anesthetic technique

Table 19-2 summarizes recommended anesthetic and surgical interventions for laparoscopy during pregnancy.

Anesthetic issues

Transvaginal ultrasound–guided oocyte retrieval (TUGOR) averages 10 to 20 minutes and can be performed with the patient under conscious sedation, paracervical block, neuraxial blockade, or general anesthesia. Therefore, short-acting agents are desired to minimize recovery time. Monitored anesthesia care and conscious sedation rely on adequate local anesthesia. However, they are inadequate to anesthetize the ovary. Patient discomfort, motion caused by pain, and a deep level of sedation leading to airway obstruction are serious risks. In addition, significant discomfort may leave patients with bad memories and may discourage future attempts at IVF. Therefore, we prefer to use neuraxial techniques or intravenous general anesthesia (IVGA).

A target-controlled propofol infusion delivered by nonanesthesiologists in the United Kingdom, initiated and supervised by a consultant anesthesiologist, required considerable medical input, especially in the early stages, to ensure the safe provision of care. Incremental alfentanil was used for analgesia. The successful use of propofol and alfentanil by patient-controlled pump was previously reported in IV sedation for egg retrieval. The main concern with propofol is distinguishing among conscious sedation, monitored anesthesia care (MAC), and general anesthesia. An anesthesiologist or nurse anesthetist under the supervision of the reproductive endocrinologist or anesthesiologist should be present at all times with the use of MAC. Therefore, it is essential to maintain verbal contact with patients during the use of conscious sedation. Even though propofol has been used by emergency medicine physicians and gastroenterologists in the United States for conscious sedation and by nonphysician providers in the United Kingdom, no data describe propofol use by nurses under reproductive endocrinologist supervision in the United States. Therefore, we discourage the practice of propofol use by nonanesthesia providers for egg retrieval.

Embryo transfer (ET) is a simple procedure that occurs on day 3 or 5 after TUGOR, relies on a fertilized oocyte, and rarely requires any anesthetic involvement. After speculum insertion into the vagina and examination of the cervix, a flexible catheter loaded with embryos and culture medium is advanced past the cervical os and injected into the uterus. Conscious sedation or MAC may be necessary in cases of significant discomfort with speculum insertion, or when there is difficulty advancing the flexible catheter past the cervical opening.

Gamete intrafallopian transfer (GIFT) is an alternative to IVF-ET that was more common before improved embryo culture techniques and successful pregnancies with IVF-ET. After hormone stimulation and TUGOR, unfertilized oocytes are mixed with sperm and transferred shortly after retrieval into the fallopian tube. Laparoscopy performed under general anesthesia is preferred so as to have direct visualization of the flexible catheter and fallopian tubes in GIFT. Although spinal anesthesia is rarely used for laparoscopic procedures because of concerns of shoulder discomfort and difficulty breathing with CO ₂ , one report highlights the safety of spinal anesthesia for laparoscopic oocyte retrieval. Another technique is performed with a minilaparoscopic approach, reducing intraperitoneal pressure and CO ₂ and obviating the need for general anesthesia. Pregnancy rates are similar between IVF-ET and GIFT; therefore the less invasive IVF-ET is more often performed. GIFT allows for the oocyte fertilization in vivo and may be acceptable for couples with religious beliefs that preclude IVF. Other transfer options include zygote intrafallopian transfer (ZIFT), pronuclear stage tubal transfer (PROST), and tubal embryo transfer (TET). Although fertilization is confirmed before embryo transfer, all these techniques require TUGOR to aspirate the follicular fluid and laparoscopically guided transfer into the fallopian tube 24 to 48 hours after fertilization. Similar pregnancy rates and the need for two procedures and anesthetics have led to a marked decline in the performance of these techniques.

In earlier reports of IVF when it was significantly longer, general endotracheal anesthesia was used with a combination of inhalation agents, with or without N ₂ O. General endotracheal anesthesia is now rarely used, except in cases of laparoscopic oocyte retrieval or when dictated by the patient's condition. Concern about the use of N ₂ O originated from earlier reports suggesting that it had a teratogenic effect and caused fetal death in rats when used during organogenesis. In addition, lower DNA and RNA content and morphologic abnormalities were demonstrated in the embryos of pregnant rats exposed to N ₂ O during organogenesis. This potential teratogenicity has been attributed in part to the inactivation of methionine synthase. Short exposures to clinical concentrations of N ₂ O, isoflurane, and halothane had no deleterious effect on IVF and early embryonic growth up to the morula stage in the mouse. Despite the deleterious effect of N ₂ O in some rat studies, no significant differences between rates of fertilization or pregnancy were demonstrated in humans undergoing laparoscopic oocyte retrieval and isoflurane/N ₂ O or isoflurane/air general anesthesia. Inhaled agents have not been shown to possess a teratogenic or embryo effect. Furthermore, halothane can protect against N ₂ O-induced teratogenicity and spontaneous abortions in rats. In addition, higher pregnancy rates have been demonstrated in women undergoing laparoscopic PROST under isoflurane/N ₂ O compared with propofol/N ₂ O anesthesia.

Propofol is an ideal induction and maintenance agent because of its short-acting half-life and antiemetic properties. However, early reports demonstrated that propofol diffuses into follicular fluid, with greater levels observed with higher doses. Even though follicular fluid concentrations are higher in the last follicle than the first follicle, no differences were found in the ratio of mature to immature follicles or in fertilization, cleavage, or embryo cell number. In addition, a report on the use of propofol for IVGA for TUGOR of donor oocytes demonstrated a lack of negative effect on the oocyte, as evaluated by cumulative embryo scores and rates of implantation and pregnancy. Use of propofol (with N ₂ O) for transfer of fertilized embryos resulted in fewer pregnancies compared with an isoflurane, N ₂ O-based anesthesia. However, higher maternal serum concentrations were needed in this study to provide anesthesia for laparoscopic PROST compared with the use of propofol for IVF-ET procedures. Another study on mouse oocytes found that high levels of propofol in the follicular fluid may affect pregnancy rates. The use of thiopental and thiamylal for laparoscopic egg retrieval has also been associated with accumulation in follicular fluid ; a comparison of thiopental and propofol used for laparoscopic GIFT demonstrated similar pregnancy rates. A case-control study comparing propofol IVGA to paracervical block showed no difference in fertilization rates, embryo cleavage characteristics, or pregnancy rates between the two groups. Neither group received premedication; both groups received 0.5 mg of alfentanil at anesthesia induction, and the propofol group received a full induction dose (2 mg/kg), followed by a continuous infusion without additional anesthetic. The results of this study are compelling because an IVGA group was compared to a local anesthetic group without premedication. In addition, no studies demonstrate a teratogenic effect of propofol. Overall, although it may appear in follicular fluid when used for IVGA for brief IVF procedures, data support that propofol has no adverse effect on pregnancy rates.

Fentanyl, alfentanil, and midazolam, when used as premedications before TUGOR, reach low intrafollicular levels and have no effect on rates of implantation or pregnancy. The absolute concentration of intrafollicular levels is extremely low compared with plasma levels. Alfentanil had the lowest follicular fluid/plasma ratio (1:40) compared with midazolam (1:20) and fentanyl (1:10). Remifentanil, a relatively new analgesic agent, has a fast onset and a very short recovery, suitable for IVF procedures. A comparison of propofol/fentanyl anesthesia to a midazolam/remifentanil technique found a decreased need for manual ventilation and a faster recovery of function in the latter group. More patients in the propofol/fentanyl group experienced intraoperative awareness and did not enjoy the anesthetic, but time to discharge did not vary. Other studies have compared a propofol-based anesthetic with a sedative combination of ketamine and midazolam without demonstrating a difference in the recovery profile, embryo transfers, or pregnancy rates. Of note, there are sparse data on the safety of ketamine or remifentanil on ART.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as IV ketorolac, would be ideal for the acute visceral pain during and after TUGOR. However, there is reluctance to use them because prostaglandins (PGE ₂ , PGF _2α , PGI ₂ ) in the embryo and endometrium are important for implantation. Prostaglandin H synthase, also known as cyclo-oxygenase (COX), is an essential enzyme in prostaglandin synthesis and primarily localized in the endometrial epithelium. Despite these concerns, no animal or human data demonstrate any changes produced by COX inhibitors on the embryo or on implantation rates. Furthermore, implantation does not occur until 3 to 5 days after egg retrieval. Some UK centers routinely use NSAIDs without any known effects on endometrial lining or implantation rates. We prefer to use NSAIDs for egg donors or for patients with pain refractory to significant doses of opioids until further data are available. Future studies should help to clarify some of these concerns.

Nausea and vomiting are the most common complications of general anesthesia but is reduced with the use of propofol, low doses of opioids, and the avoidance of inhaled anesthetic agents. We prefer to avoid metoclopramide in patients undergoing IVF; the risk of affecting embryo implantation and a successful pregnancy is greater than its benefit in patients not at significant risk for acid aspiration syndrome. Metoclopramide, a dopamine receptor antagonist, causes elevated prolactin levels that may be associated with inhibition of pulsatile gonadotropin-releasing hormone (GnRH) secretion, a hypoestrogenic state, and ovulatory dysfunction. Although not helpful for gastric motility, ondansetron use for the treatment or prevention of nausea and vomiting is not contraindicated during IVF. Serotonergic agents, unlike serotonin (5-HT ₃ ) receptor antagonists such as ondansetron, may also increase prolactin levels. We prefer to use a neuraxial technique for patients at increased risk for postoperative nausea and vomiting or acid aspiration syndrome.

During TUGOR, a transvaginal approach is used to puncture the ovary and aspirate the follicular fluid. Both sympathetic and parasympathetic nerves supply the ovaries. Although most of the sympathetic nerves are derived from the ovarian plexus that accompanies the ovarian vessels, a minority are derived from the plexus that surrounds the ovarian branch of the uterine artery. Acute visceral pain is often diffuse in distribution, vague in location of origin, and referred to remote areas of the body. Paracervical block (PCB) has been utilized with and without conscious sedation for TUGOR to improve pain relief. PCB anesthetizes the vaginal mucosa, uterosacral ligaments, and peritoneal membrane over the pouch of Douglas. Although the ovaries are not anesthetized, their pain sensitivity is the lowest compared with the rest of the internal female genital organs. PCB with 150 mg of lidocaine reduced abdominal pain by one half compared with placebo. The linear visual analog pain score (VAPS; 0-100 mm) decreased from 43.7 to 21.2 mm when evaluated 4 hours after TUGOR. Another study demonstrated no difference in VAPS when 50 mg of lidocaine was compared with 100 and 150 mg for PCB. Assessing VAPS immediately after the procedure found median abdominal pain levels of 30 to 32 mm. Although small concentrations of lidocaine in the follicular fluid can have adverse effects in mouse oocyte fertilization and embryo development, these levels do not affect embryo implantation or pregnancy rates. PCB alone is not sufficient to provide complete analgesia because of its 10% to 15% failure rate and lack of interference with afferent sensory fibers originating from the ovarian plexus. This finding is reflected in the 2.5 times higher vaginal and abdominal pain levels with PCB alone versus PCB with the addition of conscious sedation.

Neuraxial techniques have also been used for TUGOR and are more likely to anesthetize the ovary, vaginal mucosa, and peritoneal membrane. A thoracic dermatomal level of the tenth thoracic vertebra (T10) or higher is needed to anesthetize the ovaries. Spinal anesthesia is more likely to be beneficial because of its increased reliability and fast onset. It requires minimal to no conscious sedation and can be tailored to minimize high sensory levels and motor blockade. The optimal spinal anesthetic should allow adequate surgical anesthesia with minimal side effects, a fast onset, a short recovery time, and a similar rate of successful pregnancies as with other anesthetic techniques. Earlier reports described the use of 60 mg of 5% lidocaine for spinal anesthesia, but long recovery times and the finding of transient neurologic symptoms caused some concerns. In an effort to decrease recovery times and keep patients comfortable, Martin et al. decreased the dose to 45 mg of lidocaine and evaluated the benefit of adding 10 μg of fentanyl to the spinal anesthetic. A comparison of these studies demonstrated decreased time to ambulate, void, and discharge in the lower-dose lidocaine group. The addition of fentanyl to the lidocaine resulted in improved analgesia during the procedure and, postoperatively, a decreased opioid consumption and no change in side effects or ability to ambulate, void, or be discharged. The addition of increased amounts of fentanyl to the spinal technique and surgical improvements leading to shorter egg retrieval led to a further decrease in the dose of lidocaine to 30 mg.

Although we have had a good success with the subarachnoid use of 30 mg of lidocaine combined with 25 μg of fentanyl, controversy about lidocaine and transient neurologic symptoms led to the evaluation of bupivacaine as an alternative. However, a comparison of 30 mg of lidocaine with equipotent doses of bupivacaine (3.75 mg) demonstrated a longer time to micturition and recovery with bupivacaine. Of note, patients undergoing IVF procedures demonstrate decreased serum albumin and α ₁ -acid glycoprotein levels during supraphysiologic estrogen states at oocyte retrieval. This may lead to an increased free fraction of highly protein-bound drugs such as bupivacaine. However, this may only be significant when using larger doses of bupivacaine during epidural anesthesia, which is rarely used during IVF. At our institution, spinal anesthesia even with low doses of local anesthetic and opioid is associated with longer times to voiding and discharge compared with IVGA. This finding and short surgical time led us to use IVGA as our standard anesthetic for TUGOR. Spinal anesthesia with 30 mg of lidocaine and 25 μg of fentanyl is used at the patient's request, in those with significant gastroesophageal reflux disease (GERD) or morbid obesity, when the patient has eaten and the oocytes must be retrieved before spontaneous ovulation occurs, and when indicated because of severe side effects to IVGA, such as postoperative nausea and vomiting.

Male factor infertility is the most common form of infertility. New variations of IVF include direct sperm harvesting and a single sperm injection into the cytoplasm of the oocyte, called intracytoplasmic sperm injection (ICSI). ICSI has greatly increased pregnancy rates in patients with male factor infertility caused by low sperm counts and is often combined with direct sperm aspiration from the epididymis or testicular biopsy. Earlier reports described a more invasive, microepididymal sperm aspiration (MESA) with open surgical aspiration of the scrotum. Recent work has pioneered less invasive techniques, such as percutaneous epididymal sperm aspiration (PESA) and testicular epididymal sperm aspiration (TESA). These two techniques have been done under local anesthesia of the superior and inferior spermatic nerves and the genital branch of the genitofemoral nerve, without premedication. We prefer to use spinal anesthesia or IVGA for these procedures to minimize patient discomfort and movement.

Anesthetic issues

In vitro fertilization consists of different stages, including suppression therapy, stimulation therapy, trigger or ovulation therapy, egg retrieval, fertilization, postovulation therapy with progesterone, and embryo transfer. Therapy with leuprolide acetate (Lupron), a GnRH agonist, causes suppression of gonadotropins (follicle-stimulating hormone and luteinizing hormone) and results in a lack of production of estrogen and progesterone. Stimulation therapy is conducted with FSH- and LH-containing human menopausal gonadotropin (hMG) and causes ovarian follicle growth. Human chorionic gonadotropin (hCG) causes ovulation to occur within 36 hours, and TUGOR is performed at this time. Supplemental progesterone is given after embryo transfer.

Stimulation therapy with gonadotropins (e.g., hMG or FSH preparations) may lead to very high estrogen levels and ovarian hyperstimulation. High estrogen levels place patients at risk for thromboembolic phenomena. In its more severe form, ovarian hyperstimulation syndrome (OHSS) may lead to increased vascular permeability with leaky capillaries and findings such as weight gain, intravascular volume depletion, ascites, pleural effusions, electrolyte changes, and renal dysfunction. These patients usually experience a state of fibrinolysis, with higher fibrinogen, plasmin/α ₂ -antiplasmin, thrombin/antithrombin complexes, and d -dimer levels than women with lower estrogen levels. In addition, tissue factor increases with high estrogen levels and is a powerful trigger of the extrinsic pathway of the coagulation cascade. Treatment is usually supportive, with intravascular volume expansion, analgesics, bed rest, and thrombosis prophylaxis. More invasive methods, such as paracentesis and thoracentesis, are more helpful for relief of symptoms, such as abdominal pain and shortness of breath. Conscious sedation is often required for these procedures and should take into account the increased sensitivity to medications caused by intravascular volume contraction. Caution should be used if regional anesthetic techniques are a consideration for these patients, because of the potential for anticoagulation.

The retrieval of oocytes from the follicles is not considered an elective procedure; failure to retrieve them may lead to spontaneous ovulation and a wasted cycle. In addition, failure to empty the follicles may lead to OHSS with all its known complications. Our preference is to perform TUGOR under spinal anesthesia with minimal sedation in patients who did not follow preoperative fasting guidelines. Aspiration prophylaxis is recommended with sodium citrate and metoclopramide, despite the concerns for increased prolactin levels with metoclopramide.

Although the rate of success continues to increase with ARTs, a significant number of cycles still do not result in a live birth. Therefore, close scrutiny is expected of variables that may affect oocyte retrieval or embryo transfer. It is essential to understand the impact of different anesthetic techniques and medications on IVF and carefully study any data that links these factors with implantation or pregnancy rates. The anesthetic may have an impact on ART, and vice versa.