OHSS management depends on the severity of the condition, and can be performed on an out-patient basis in the mild forms, or in the hospital setting in the intensive therapy unit in the severe cases. VTE events, renal failure not responding to treatment and pulmonary compromise are indications for ITU care [6]. As the condition is most often self-limiting, reassurance has to be given to the woman and her partner. In extremely severe and protracted cases, when supportive treatment is not sufficient, termination of the pregnancy in order to decrease the circulating hCG levels may be necessary.

According to the RCOG, mild to moderate OHSS can be managed on an outpatient basis, with paracetamol and codeine used for pain control. Drinking to thirst is encouraged [25] and avoidance of strenuous exercise and intercourse is advised. Clinical assessment including body weight recording, abdominal girth measurement and pelvic ultrasound should be carried out every 2–3 days in order to determine deterioration of condition [14]. In more severe cases, multidisciplinary inpatient approach to treatment should be considered. When abdominal distension due to ascites causes severe discomfort or impedes respiration, ultrasound guided paracentesis should be considered [26, 27]. Similarly, women with inadequate urine output despite appropriate parenteral rehydration and ascites could benefit from decreased intra-abdominal pressure, as this might improve renal circulation and restore urine production [28]. Cardiovascular collapse due to rapid fluid shifts can be avoided by gradual drainage of ascites and the use of pigtail catheters [29]. Thromboprophylaxis should be considered in all women admitted to hospital due to OHSS in order to minimize the incidence of VTE [14].

Transvaginal ultrasound guided oocyte retrieval (TVOR) is currently the procedure of choice for oocyte collection in most IVF centres worldwide [30]. Though the procedure is deemed safe, there are associated risks related to bleeding and intraabdominal sepsis.

Loss of pregnancy before the arbitrary gestation of viability (24 completed weeks) is defined as a miscarriage. Multiple studies have reported an increased risk of miscarriage in the ART population with the prevalence of 17–32.6 % [4, 45]. When analysing these reports in the context of miscarrige, it is important to differentiate the causes of underlying subfertility and the risk of ART per se. Infertile couples are more likely to be older (5 years on average) than their fertile counterparts, are more likely to have endocrine disorders (thyroid dysfunction and PCOS) and/or structural uterine anomalies [46–49]. The intense surveillance of ART pregnancies and very early serum testing for implantation, might also contribute to the relatively high prevalence of very early ART pregnancy losses, when compared to less monitored spontaneous conceptions.

A retrospective study by Pezeshki et al. in 2000 has demonstrated a miscarriage rate of 21.3 % in the ovulation induction population, 19.8 % in the IVF population and 26.2 % after spontaneous conception. Maternal age was the most significant predictor of miscarriage, but the cause of infertility did not play an important role in the miscarriage risk [50]. Comparison of ART pregnancies with historical data on spontaneous conceptions has revealed that the unadjusted relative risk of miscarriage following ART was 1.33–1.49 (95 % CI 1.08–1.68), with maternal age being a significant contributor. Intense stimulation protocols and high estradiol levels (>8 nmol/L) were associated with an increased risk of miscarriage (23 % versus 10 % when estradiol was <2 nmol/L) [51]. In the above-mentioned study, the authors have reported a significant difference in the first and second trimester miscarriage rates between the ART and historical control cohorts. The authors concluded that maternal age, history of previous miscarriage and ‘some’ treatment related factors might be responsible for the observed increase in miscarriage rates, with further studies required to validate the statement [51]. Overall, miscarriage rates in ART pregnancies are similar or marginally higher when compared to spontaneous conceptions.

Development of a pregnancy outside of the endometrial cavity can be broadly termed as an ectopic pregnancy (EP). Multiple implantation sites of an early pregnancy are possible, including the Fallopian tubes, ovaries, the cervix, cesarean section scar, interstitial portions of the tube, and the abdominal cavity, with Fallopian tubes being the most frequent site. Contemporaneous existence of an ectopic and an intrauterine gestation is termed a heterotopic pregnancy. Approximately 1 % of all spontaneously conceived pregnancies develop as an ectopic pregnancy. The incidence of heterotopic pregnancies in the general population is estimated to be 1 in 20,000 to 1 in 50,000 pregnancies. In the ART setting, this can be as frequent as 1 in 100 [52].

The overall trend of ectopic gestations is on the increase. This is thought to be related to an increasing prevalence of pelvic infections caused by such pathogens as Chlamydia trachomatis and Neisseria gonorrhea, as well as the wide spread use of ART. The incidence of ectopic pregnancies associated with ART with an embryo transfer performed is approximately 1–5 % [53]. In view of the high frequency of occurrence of this potentially fatal condition, an early transvaginal scan is recommended in all women undergoing IVF or ICSI. This should be routinely performed between 6 and 8 weeks gestation [53]. The clinical manifestations of an ectopic pregnancy can vary greatly, with the initial symptoms developing as early as the 5th week of gestation, or as late as the 12th week [54]. Asymptomatic patients are diagnosed during and ultrasound scan; however, symptomatic cases can present with a significant intra-abdominal haemorrhage and signs of hypovolaemic shock requiring immediate surgery (Fig. 5.3).

In the case of ART, when patients present with abdominal pain and a positive pregnancy test, the differential diagnoses need to include ovarian hyperstimulation syndrome with possible adnexal torsion and ectopic pregnancy. The timing of presentation in relation to the ART procedures might aid in making one or the other diagnosis likely. It is also worth remembering, that the hCG used to trigger final oocyte maturation might produce a positive pregnancy test result if performed within 12 days of administration of 5000 units of hCG [55].

Multifetal pregnancy rates following ART range from 5 to 40 % [56]. Dichorionic twin pregnancies are the most common form of multiple gestation following ART; however, monozygotic and monochorionic pregnancy rate in the IVF population is estimated at 0.9–2 %, compared to 0.4 % of spontaneous conceptions [57–59]. Higher order pregnancies (triplet or more) in approximately two-third of cases are the result of ovulation induction without the use of IVF or any similar procedure [60]. See Fig. 5.4a–d.

Blastocyst transfers contribute to the increase of multiple gestations, as embryo splitting at this stage can occur in 6 % of cases [61]. During IVF treatment, irrespective of age, transfer of a single blastocyst stage embryo carries a less than 2 % multiple gestation risk. For a double blastocyst embryo transfer, the risk approximates 39 %, whereas a double cleavage stage embryo transfer carries a 27 % risk of multiple gestation [62]. Preterm birth associated with multiple gestations is deemed as one of the most important adverse outcomes following ART. Care for such neonates incurs significant costs to the healthcare systems with the long-term outcomes of such babies being difficult to predict. Neonatal intensive care unit (NICU) admissions in 12–17 % of cases are related to multiple pregnancies, with up to 91 % of these related to IVF, where two to six embryos were transferred [63]. Most systematic reviews on outcomes of ART pregnancies indicate statistically better pregnancy outcomes for ART twins compared to spontaneous conceptions. This is in contrast to singleton pregnancies, where natural singletons perform better compared to ART conceived infants [5]. However, depending on the study and populations assessed, preterm birth, low birth weight and congenital anomalies can be either similar or worse in the ART population compared to spontaneously conceived multiple gestations [64, 65]. A systematic review of a total of 4385 ART twin pregnancies and 11,793 spontaneous twin gestations indicates an increased risk of preterm birth and low birth weight of <2500 g in ART pregnancies (RR 1.23, 95 % CI 1.09–1.41 and RR 1.14, 95 % CI 1.06–1.22, respectively) [66]. Maternal anaemia, pregnancy associated hypertensive disorders, gestational diabetes, caesarean section rates and post partum haemorrhage are a well-known risk of multiple gestations. With increasing prevalence of multiple pregnancies, these complications are a more frequent event on the current labour ward.