The incidence of major clinical complications in a Dutch transport IVF programme

Four different major clinical complications were identifiedin a retrospective analysis of 2495 in-vitro fertilization (IVF)cycles resulting in oocyte retrieval. The severe form of ovarianhyperstimulation syndrome (OHSS) occurred in 18 patients, givinga prevalence for this complication of 0.7%. Seven (39%) of these18 patients had previously been diagnosed as having polycysticovaries. Eleven patients were admitted with moderate OHSS. Adnexaltorsion was diagnosed in two patients. Ovariectomy was considerednecessary in both cases. Complications of the transvaginal procedureoccurred in seven cases (0.3%): one patient had an acute appendicitiswith puncture holes in the appendix, six patients were admittedshortly after oocyte retrieval with a pelvic inflammatory disease.Of the 624 pregnancies obtained, 13 were ectopic, giving anectopic pregnancy rate of 2.1%. It is concluded that seriousclinical complications of IVF treatment are rare. However, patientsshould be counselled for the occurrence of serious procedure-relatedcomplications before entering an IVF programme.     

Acute ureteral obstruction following transvaginal oocyte retrieval for IVF.

Transvaginal, ultrasound-guided oocyte retrieval has become the gold standard for IVF therapy. Despite a low reported complication rate, here a case is reported of acute ureteral obstruction following seemingly uncomplicated oocyte retrieval. Prompt diagnosis and ureteral stenting led to rapid patient recovery with no long-term urinary tract sequelae. Ureteral injury needs to be included in the differential diagnosis of a patient presenting with pelvic/abdominal pain following oocyte retrieval.     

The effect of insemination/injection time on the results of IVF and ICSI

BACKGROUND: The aim of this study was to investigate whether a pre-incubation time between oocyte retrieval and insemination or injection had any effect on the success rate of IVF or intracytoplasmic sperm injection (ICSI). Based on previously published data, many laboratories retain a time interval of several hours between oocyte retrieval and insemination/injection. In our setting, insemination and injection times are dependent only on the laboratory workload. METHODS: Totals of 881 IVF and 432 ICSI cycles performed between 1997 and 1999 were analysed retrospectively. Oocyte retrieval occurred 36 h after human chorionic gonadotrophin administration, and insemination or injection took place 1--7 or 0.5--8 h after oocyte retrieval respectively. RESULTS: No statistically significant differences were found between these time periods and outcome of IVF and ICSI with respect to fertilization rate, embryo quality, implantation rate, abortion and ongoing pregnancy rates, except for the abortion rate after IVF. As this finding may be due to chance and no differences were found in the ongoing pregnancy rates, this finding was considered to be of less importance. CONCLUSIONS: If laboratory control and efficiency demands early insemination or injection, it could be performed without reservation.     

Ejaculation failure on the day of oocyte retrieval for IVF: case report

Unexpected ejaculation failure on the day of oocyte retrieval for IVF occurs once or twice a year in our Reproductive Medicine Unit, where approximately 500 oocyte retrievals are performed each year. Two clinical situations which occurred in 2001 are presented. In the first case, sperm were finally obtained by epididymal aspiration and resulted in the fertilization of five oocytes by ICSI. The transfer of two fresh embryos did not result in a pregnancy and the three supernumerary zygotes were cryopreserved. The male patient presented an anxio-depressive episode necessitating psychiatric hospitalization 1 week after the oocyte retrieval. In the second case, no sperm were obtained and the four oocytes were therefore lost. The couple went through a crisis in their relationship and tried another cycle of IVF 10 months later, after the preventive cryopreservation of a sperm sample. On the day of oocyte retrieval the patient was unable to produce a fresh sample but three zygotes were obtained through ICSI using the back-up cryopreserved sperm. Two embryos were transferred but no pregnancy ensued. The clinical decision-making processes for these two cases are described, as well as the measures employed to help prevent these unfortunate situations.     

Is intracytoplasmic sperm injection (ICSI) a safe procedure? What do we learn from early pregnancy data about ICSI?

The aim of this study was to evaluate the safety of the intracytoplasmicsperm injection (ICSI) procedure by analysing early pregnancydata from ICSI and in-vitro fertilization (IVF) patients. Inall, 50 ICSI pregnancies were compared with 226 FVF pregnancies.Comparisons were made during the first 9 weeks after the theoreticallast menstrual period (7 weeks after oocyte retrieval) withregard to epidemiological data, plasma hormonal concentrationsand transvaginal ultrasonographical findings. Although patientswere significantly (P < 0.001) younger in ICSI (31 years)than in IVF pregnancies (33 years), their duration of infertilitywas similar. Miscarriage and multiple gestation rates were notsignificantly different in ICSI pregnancies (respectively 24and 24%) from those found after IVF (32 and 29%). The probabilityof developmental arrest of the intrauterine sac (miscarriagesand vanishing twins) was similar in both ICSI (16%) and IVF(25%) cases. The mean plasma hormonal concentrations startingfrom day 11 after oocyte retrieval were similar in both groups.Every ICSI and IVF pregnancy showed an embryo with cardiac activityat 7 weeks. Early pregnancy data did not show any abnormal findingsfor pregnancies achieved using ICSI compared to those achievedby FVF.     

Pregnancies after activated oocyte transfer: a new option for infertility treatment.

In this preliminary report, we describe a new technique involving the same-day transfer of activated oocytes to the uterus after intracytoplasmatic sperm injection (ICSI). The technique, termed activated oocyte transfer (AOT), offered to 19 couples, yielded a pregnancy rate per cycle of about 30%, equivalent to traditional in-vitro fertilization (IVF) and ICSI in a laboratory setting. AOT is performed 4 h after oocyte retrieval, permitting the patient to undergo treatment as an out-patient procedure.     

Maternal serum ghrelin levels in early IVF pregnancies: lack of prognostic value for viable pregnancy and altered post-prandial responses

BACKGROUND: Ghrelin is a pleiotropic hormone, involved in the control ofgrowth and metabolism, whose circulating levels fluctuate inrelation to food intake and body mass index. Ghrelin has beendetected in the decidualized endometrium, as well as in humanand rat placenta. METHODS: A total of 106 patients undergoing IVF procedures were prospectivelyrecruited. On Days 16 and 23 after oocyte retrieval, the patientswere subjected to blood sampling after overnight fasting, fordetermination of serum ghrelin, hCGβ and progesterone levels.In addition, ghrelin levels were assayed in these groups, 2h after ingestion of a fixed-calorie meal. RESULTS: The subjects were divided according to whether they achievedan ongoing pregnancy. On Days 16 and 23 after oocyte retrieval,pre-prandial serum ghrelin levels were not statistically different,although a general trend toward a decrease in circulating ghrelinby Day 23 was detected in pregnant groups. Although in non-conceivingsubjects, maternal ghrelin levels showed an expected 15% declineafter meal ingestion, such a post-prandial decrease was notstatistically significant in pregnant women, selectively onDay 16 after oocyte retrieval. CONCLUSIONS: Maternal ghrelin levels at early gestational age do not appearto pose diagnostic (as marker) or prognostic value for pregnancyoutcome in IVF procedures.     

Timed oocyte collection in an assisted conception programme using GnRH analogue

Three-hundred-and-twenty-five patients on an assisted conception programme underwent 378 cycles of oocyte retrieval (OPU) following ovarian stimulation using a GnRH analogue and human menopausal gonadotrophins (HMG), a regimen which allows programmed cycles and delayed oocyte retrieval. Eighteen cycles were excluded (failed OPU in three and failure of fertilization in 15). In 360 cycles, patients completed their treatment with either in-vitro fertilization/embryo transfer (IVF/ET) (116) or gamete intra-Fallopian transfer (GIFT) (244), of which 241 took place at the normal time and 119 were delayed for 24 h or more to avoid weekend operating. The overall pregnancy rate per OPU was 29.5%, with the IVF group being 24.1% and the GIFT group being 32.8%. In the group of patients in whom OPU was delayed, the pregnancy rate was significantly higher in each sub-group than in the corresponding non-delayed sub-group (overall, 37.0 versus 25.7%; IVF/ET, 38.5 versus 16.9%; GIFT, 36.3 versus 31.1%). There was a significantly higher number of oocytes collected, gametes/embryos transferred in the group whose OPU had been delayed. In patients receiving GnRH analogue and HMG for ovarian stimulation, delaying oocyte retrieval is not harmful, may result in an improved outcome and allows OPU to be performed on routine operating lists. This facility, together with the improved pregnancy rates associated with this protocol of ovarian stimulation should improve the cost-effectiveness of assisted conception programmes.     

Timing luteal phase support in GnRH agonist down-regulated IVF/embryo transfer cycles

BACKGROUND: The aim of this study was to compare the effect of three different times of onset of luteal phase support on ongoing pregnancy rate in infertile patients undergoing treatment with GnRH down-regulated IVF and embryo transfer (IVF/ET). MATERIALS AND METHODS: All consecutive eligible patients planned to undergo their first IVF treatment cycle were randomly allocated to receive vaginal progesterone as luteal support at three different time points, that is, after HCG administration for final oocyte maturation (HCG group), at the day of oocyte retrieval (OR group) or at the day of ET (ET group). The primary endpoint of this study was ongoing pregnancy rate. RESULTS: A total of 385 women were randomized, 130 were allocated to the HCG group, 128 to the OR group and 127 to the ET group. An ongoing pregnancy rate of 20.8% was found in the HCG group versus 22.7 and 23.6% in the OR group and ET group, respectively. The mean number and quality of the retrieved oocytes and the transferred embryos did not differ. CONCLUSION: Based on this data, an 18% difference in ongoing pregnancy rate between the three different times of onset of luteal phase support in GnRH agonist down-regulated IVF/ET cycles can be refuted. Smaller clinically meaningful differences may be present.     

Infertility: Natural cycles for in-vitro fertilization: cost-effectiveness analysis and factors influencing outcome

Improvements in oocyte culture technique, sperm preparation,oocyte retrieval method and ovarian stimulation regimens haveproduced higher pregnancy rates with in-vitro fertilization(IVF) treatment. However, because ovarian stimulation is expensiveand not without risk, there is increasing interest in the optionof using natural cycles for IVF. This study was performed todocument the experience and outcome in 240 natural cycles. Cancellationoccurred in 28 cycles (12%), and LH surge was observed in 56(23%), leaving 156 (65%) cycles which progressed to oocyte retrieval.No oocytes were retrieved in 26 cycles. Among the successfuloocyte retrievals, the majority yielded one oocyte. There wasno evidence of fertilization in 26 cases, and triploid fertilizationwas observed in 12 cases. Embryos suitable for transfer wereavailable in 92 cycles in which 11 (12%) clinical pregnancieswere confirmed. Despite the high failure rate at each step inthe process, natural cycles are more cost-effective than stimulatedcycles which incur an incremental cost per live birth of $48000. Natural cycles offer a low-cost alternative that may bemore accessible to patients.     

Ultrasound-guided aspiration of hydrosalpinges is associated with improved pregnancy and implantation rates after in-vitro fertilization cycles

Previous reports have shown that the presence of hydrosalpinges may have a detrimental effect on in-vitro fertilization (IVF) outcomes and salpingectomy has been recommended by some authors as a means of improving IVF pregnancy rates. Our first objective was to determine the effect of hydrosalpinges diagnosed by ultrasound on IVF outcomes in our clinic. Our second objective was to examine the effects of aspiration of hydrosalpinges at the time of oocyte retrieval on IVF outcomes. Women with hydrosalpinges (n=34) were compared with women who had tubal disease but no hydrosalpinges (n=124) and were found to have a reduced clinical pregnancy rate (18 % versus 37%, P=0.053), a reduced ongoing pregnancy rate (15 versus 34%, P=0.051), and a reduced implantation rate (7 versus 18%, P=0.003) after IVF procedures. Among women with hydrosalpinges present, 16 had their hydrosalpinges aspirated at the time of oocyte retrieval and 18 did not. Aspiration of hydrosalpinges was associated with a higher clinical pregnancy rate (31 versus 5%, P=0.07), a higher ongoing pregnancy rate (31 versus 0%, P=0.015), and a higher implantation rate (14 versus 1%, P=0.015). This study confirms the association between the presence of hydrosalpinges and poor IVF outcomes. We find that aspiration of hydrosalpinges at the time of oocyte retrieval leads to improved pregnancy rates and may be an acceptable alternative to salpingectomy for treatment of these patients.      

Day 14 maternal serum progesterone levels predict pregnancy outcome in IVF/ICSI treatment cycles: a prospective study

BACKGROUND: Serum progesterone has been advocated as a tool in the diagnosis of early pregnancy failure. We conducted this prospective study in order to investigate the potential value of early (14 days after oocyte recovery) serum progesterone measurement, in women undergoing IVF/ICSI and receiving rectal progesterone supplements, in relation to pregnancy outcome. METHODS: 442 women consecutively treated by IVF or ICSI had serum progesterone and bhCG levels prospectively measured 14 days after oocyte retrieval (day 0). All women received natural progesterone 400 mg rectally until the pregnancy test on day 14. Pregnant women were followed up by serial transvaginal ultrasound scans to 8 weeks gestation. RESULTS: 115 women (26%) had a viable intra-uterine pregnancy at 8 weeks gestation, 80 (18.1%) had an abnormal pregnancy (biochemical, ectopic, miscarriage) and 247 (55.9%) failed to conceive. Women with on-going pregnancies had significantly higher serum progesterone levels (median: 430, 95%CI: 390-500 nmol/l) compared to those who had either an abnormal pregnancy (72, 48-96 nmol/l; P < 0.001) or failed to conceive (33, 28-37 nmol/l; P < 0.001). Receiver-operator curve analysis demonstrated that a single serum progesterone on day 14 post-oocyte retrieval, could highly differentiate between normal and abnormal pregnancies (area under the curve = 0.927, 95%CI = 0.89-0.96; P < 0.0001). CONCLUSIONS: In spite of exogenous progesterone supplementation, serum progesterone levels, from as early as 4 weeks gestation (day 14 post-oocyte retrieval) were significantly elevated and predicted women destined to have viable intra-uterine pregnancies. These high levels are suggestive that endogenous progesterone is already sufficient in viable pregnancies and that exogenous progesterone administration will not rescue a pregnancy destined to result in a miscarriage. Single serum progesterone measurement could be a useful indicator of pregnancy outcome in women undergoing IVF or ICSI treatment.     

Stress and outcome success in IVF: the role of self-reports and endocrine variables

BACKGROUND: The aim of this study was to examine the associations between urinary levels of the stress hormones adrenaline, noradrenaline and cortisol during treatment with self reported stress, in order to investigate the mechanism for the previously observed negative association of anxiety and depression with the outcome of IVF/ICSI. METHODS: In a multicentre prospective cohort study, women entering their first cycle of IVF/ICSI treatment were asked to participate. From each participant nocturnal urine samples were collected; pre-treatment, before oocyte retrieval and before embryo-transfer (ET), to assess hormonal concentrations. Additionally, two questionnaires were administered before the start of the treatment to measure anxiety and depression. RESULTS: 168 women completed the questionnaires and collected at least two urine specimens. A significant positive correlation between urinary adrenaline concentrations at baseline and ET and the scores on depression at baseline were found. In women with successful treatment, lower concentrations of adrenaline at oocyte retrieval and lower concentrations of adrenaline and noradrenaline at ET, compared with unsuccessful women, were found. CONCLUSIONS: The significant positive association of adrenaline concentration with pregnancy and with depression suggested that this adrenal hormone could be one of the links in the complex relationship between psychosocial stress and outcome after IVF/ICSI.     

A prospective randomized study: day 2 versus day 5 embryo transfer

BACKGROUND: This randomized controlled study was performed in an unselected IVF/ICSI population to test the hypothesis that blastocyst transfers result in higher clinical pregnancy rates (CPR) per oocyte retrieval when compared with day 2 transfers. METHODS: Blind randomization for transfer on day 2 (group 1) or day 5/6 (group 2) was performed before stimulation. Oocytes and embryos were cultured in sequential media in 5.5% CO(2), 5% O(2), 89.5% N(2) and 90% humidity. A maximum of two embryos was transferred. RESULTS: The two groups were similar for age, IVF indication, number of treatment cycles, rate of ICSI/IVF, number of fertilized oocytes and number of embryos transferred. The CPR/oocyte retrieval was comparable in group 1 (32%) and in group 2 (44%), while the CPR/embryo transfer was significantly higher (P < 0.01) in group 2 (60%) than in group 1 (35%). Similarly, the implantation rate per embryo transferred was significantly higher (P < 0.03) in group 2 (46%) than in group 1 (29%). The cryo-augmented delivery rate/oocyte retrieval was comparable in group 2 (36.3%) and in group 1 (28.6%). CONCLUSION: This randomized study in an unselected population showed a significantly higher CPR/embryo transfer and a tendency toward a higher CPR/oocyte retrieval in patients receiving blastocysts when compared with day 2 transfers.     

Physiology: Follicular volume and number during in-vitro fertilization: association with oocyte developmental capacity and pregnancy rate

This study examined the effect of the number of follicles aspiratedduring egg retrieval on pregnancy likelihood during an ovulationinduction, in-vitro fertilization (IVF) programme. In addition,the volume of each individual follicle was related to the probabilityof obtaining an oocyte from that follicle. Its capacity to befertilized, the incidence of polyspermic fertilization, thequality of early embryos derived from that oocyte and the influenceof patient age were the other outcomes studied. Large follicularnumber and high mean follicular volume related positively topregnancy outcome. Successful egg retrieval, normal fertilizationand good embryo quality were more likely with increasing individualfollicular volume. A model was constructed to quantify the predictivevalue of follicular fluid volume on the developmental potentialof individual oocytes and embryos derived from that follicle.Successful outcome of IVF is more likely if ovulation inductionresults in many follicles, particularly if they have a highmean volume. Individual oocyte and embryo quality can be tracedback to the follicular level.     

Ratio of oestradiol concentration on the day of human chorionic gonadotrophin administration to mid-luteal oestradiol concentration is predictive of in-vitro fertilization outcome.

The role of luteal oestradiol for successful implantation in humans seems to be permissive rather than obligatory. Few studies have attempted to clarify the role of early luteal oestradiol in in-vitro fertilization (IVF) outcome, whether peri-implantation oestradiol is predictive of successful IVF outcome. We retrospectively analysed 106 women undergoing 106 IVF/embryo transfer cycles. Only the first treatment cycle per patient was analysed. Peak oestradiol denoted the concentration on the day of human chorionic gonadotrophin (HCG) administration. Mid-luteal oestradiol was obtained 3 days after embryo transfer (8 days after HCG administration). A total of 44 pregnancies were noted (41.51%). There were no differences in age, cycle day 3 follicle stimulating hormone (FSH), peak oestradiol, number of retrieved oocytes, number of embryo transfers, and mid-luteal oestradiol between pregnant and non-pregnant women. However, the ratio of day of HCG oestradiol to mid-luteal oestradiol was highly predictive of successful outcome: the ongoing pregnancy rate and implantation rate (sacs with fetal heart beat/embryo transfer) were 15.8 and 5.7% respectively if the above ratio exceeded 5.0 (n = 19), compared to 42.1 and 16.3%, and 53.3 and 26. 5% if the ratio was between 0.4 and 2.5 (n = 57), and between 2.5 and 5.0 (n = 30) respectively. Our study suggests that the magnitude of decline in oestradiol concentrations after oocyte retrieval may be important in predicting IVF success. We postulate that endometrial integrity may become compromised when a dramatic drop in oestradiol occurs by the mid-luteal period. Whether these women benefit from oestradiol supplementation after oocyte retrieval remains to be investigated.     

Pre-ovarian block versus paracervical block for oocyte retrieval

BACKGROUND: A pre-ovarian block (POB) technique can be used for pain relief during oocyte retrieval in IVF. The local anaesthetic is deposited in the vaginal wall and between the vaginal wall and the peritoneal surface near the ovary using ultrasound guidance. The aim of this study was to test whether analgesia with POB resulted in improved pain relief compared to paracervical block (PCB). METHODS: A prospective, randomized, multicentre study of POB versus PCB (10 ml of 1% lidocaine each) with 183 patients randomized to POB (n = 96) or PCB (n = 87) was performed. Randomization (via a computer-generated list) was balanced for age, previously completed IVF cycles, degree of anxiety, estimated number of follicles, BMI, premedication and centre. Pain was measured using a visual analogue scale (VAS, 0-100 mm) and given as median values. The primary end-point of this study was overall VAS pain score for both sides during the oocyte retrieval procedure. RESULTS: Overall pain during the entire oocyte retrieval was 22 (POB) and 16 (PCB) (P = 0.42). No differences were found in degree of anxiety, premedication, dose of alfentanil, fertilization rate, number of good-quality embryos or clinical pregnancy rate. CONCLUSIONS: No differences were found in overall pain experienced during the entire oocyte retrieval procedure with POB compared to PCB.     

Uro-retroperitoneum after ultrasound-guided transvaginal follicle puncture in an oocyte donor: a case report

Ultrasound-guided transvaginal follicle aspiration is the standard technique for oocyte retrieval prior to IVF. Complications are rare, but some are potentially serious. We report a case of ureteral injury with acute-onset uro-retroperitoneum in a volunteer oocyte donor. The patient recovered rapidly after ureteral stenting. This case underlines the need for all candidate oocyte donors to receive proper information on serious procedure-related complications.     

The role of oocyte donation in women who are unsuccessful with in-vitro fertilization treatment.

Oocyte donation improves the chances of becoming pregnant in some women who are unsuccessful with in-vitro fertilization (IVF) treatment. A total of 119 IVF cycles achieved a pregnancy rate per cycle of 2.5% whereas the same women, when treated with 45 cycles of oocyte donation, achieved a 24.5% pregnancy rate per cycle. To ascertain which women may be helped by oocyte donation, IVF data were analysed according to the outcome of oocyte donation. There was a difference in the number of previous natural conceptions and live births, and in the IVF fertilization rate. There was no difference in the age of the women and the numbers of oocytes collected per cycle of IVF. New criteria are therefore suggested for recommending oocyte donation to women who have previously failed to become pregnant with IVF treatment.     

Infertility: CASE REPORT: Acute abdomen following dermoid cyst rupture during transvaginal ultrasonographically guided retrieval of oocytes

We report a case of acute abdomen due to puncture of a dermoidcyst during oocyte aspiration, which required laparotomy. Awoman who had undergone an in-vitro fertilization and embryotransfer required hospitalization due to onset of an acute abdomen.An ultrasonographic scan showed a pelvic mass with the featuresof dermoid cyst The patient required diagnostic laparotomy whichconfirmed the presence of a ruptured dermoid cyst with subsequentperitonitis.