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[Ovarian hyperstimulation syndrome in medically assisted reproduction].

Ovarian hyperstimulation syndrome (OHS) is the most serious complication of ovulation induction, particularly in in vitro fertilization. It is a potentially life-threatening situation. Its pathophysiology is poorly understood. This syndrome is explained by a sudden increase in capillary permeability which results in a rapid fluid shift from the intravascular space into a third space leading to haemodynamic changes. In its most severe forms. OHS is characterized by multicystic ovarian enlargement, hemoconcentration, hypovolemia, oliguria, third space accumulation of fluid in the form of ascites and pleural effusion, renal failure, thrombotic disorders. Mild and the most of moderate forms of OHS usually do not require any active form of therapy. Severe OHS requires hospitalization, correction of fluid and electrolyte imbalance, prevention of thromboembolism, aspiration of the ascites and pleural effusion causing respiratory discomfort and dyspnea. Surgical interventions are exceptionally indicated and reserved for ovarian or rupture of ovarian cyst. Although severe OHS may not be completely avoided, early recognition of high-risk factors, judicious monitoring of ovulation induction (plasma estradiol levels and ultrasonography), and, perhaps in future, substitution of hCG for triggering ovulation should reduce the incidence of this iatrogenic syndrome.

Clinical Protocols↗

The genetics of flower development: from floral induction to ovule morphogenesis.

Flower development consists of several phases. The first step is the transition from vegetative to reproductive development, regulated by floral induction. Later steps include the initiation of individual flowers, the determination of organ identity, and organ-specific differentiation. One of the major discoveries of plant biology is that the genetic network controlling flower development is highly conserved in two distantly related dicots, Arabidopsis thaliana and Antirrhinum majus, and probably in other species as well. Classical genetics has identified a sizable number of genes regulating flower development, and many of these regulatory genes have been cloned. This review summarizes recent advances in the understanding of the genetic control of floral induction and determination of flower-meristem identity, with the focus on Arabidopsis thaliana. In addition, recent work on ovule morphogenesis, a late process in flower development, is discussed.

Arabidopsis↗

Bilateral internal jugular venous thrombosis complicating severe ovarian hyperstimulation syndrome after prophylactic albumin administration.

OBJECTIVE: To report a case of bilateral thrombosis of the internal jugular veins in a patient after controlled ovarian hyperstimulation and IVF. DESIGN: Case report. SETTING: University-based IVF program. INTERVENTION(S): Ovulation induction with gonadotropins, IVF-ET, albumin administration, and therapeutic heparinization. MAIN OUTCOME MEASURE(S): Doppler ultrasound of neck veins. RESULT(S): Severe ovarian hyperstimulation syndrome and bilateral thrombosis of the internal jugular veins occurred despite prophylactic administration of albumin. This was treated successfully with therapeutic heparinization. CONCLUSION(S): Internal jugular venous thrombosis, a rare complication of ovulation induction with gonadotropins, should be considered in patients with neck pain and swelling.

Adult↗

Serum placental protein 14 concentrations are similar in the first trimester pregnancies of women after pituitary down-regulation with a gonadotrophin-releasing hormone agonist and normal cycles with frozen embryo transfers.

Previous studies suggest that, in pregnancies after in-vitro fertilization (IVF) and embryo transfer following pituitary down-regulation with a gonadotrophin-releasing hormone analogue (buserelin) and ovulation induction with human gonadotrophins, the serum placental protein 14 (PP14) concentration is lower than in normally conceived pregnancies. We studied serum PP14 concentrations in two groups of women: (i) in 17 infertile women whose pregnancy followed IVF and embryo transfer using buserelin (long protocol) and human menopausal gonadotrophin for ovulation induction; (ii) in 15 women whose pregnancy followed transfer of frozen-thawed embryos. Similar PP14 concentrations were found in both groups on days 9-10, 14-15 and 70-77 after human chorionic gonadotrophin administration (buserelin, IVF/embryo transfer) or spontaneous luteinizing hormone surge (frozen-thawed embryo transfer). Our results show that PP14 secretion is not compromised by pituitary down-regulation with buserelin in infertile women with functional ovaries.

Buserelin↗

The effect of age on the ovarian response to gonadotropin and on pregnancy rate in polycystic ovary syndrome.

Recent studies have proposed that, in women affected by the polycystic ovary syndrome (PCOS), aging is able to regularize the menstrual cyclicity. To evaluate the ovarian response in PCOS patients according to their age, we studied 33 PCOS patients, 20 of whom with an age ranging from 28 to 34 years (younger PCOS) and 13 ranging from 35 to 45 years (older PCOS). All patients underwent an ovulation induction therapeutic protocol with low-dose recombinant follicle stimulating hormone, for a total of 80 cycles (44 cycles for the younger PCOS group and 36 cycles for the older PCOS group). No significant difference was found between the days of therapy (12.3 +/- 5.4 vs. 13.5 +/- 5.6 days), total amount of drugs (980.7 +/- 568.9 IU vs. 1063.9 +/- 469.5 IU) or ovulation rate (93% vs. 89%) in the two groups. The two groups showed a significant difference in the maximum estradiol level (2053.5 +/- 1497.2 vs. 1269.0 +/- 911.5 pmol/l, p < 0.01), the number of the recruited and preovulatory follicles (1.7 +/- 2.5 vs. 0.64 +/- 0.9, p < 0.05 and 1.7 +/- 1.1 vs. 1.2 +/- 0.5, p < 0.01, respectively) and the pregnancy rate (36% vs. 14%, p < 0.05). In conclusion, our data clearly showed that, also in PCOS, advanced age is a negative prognostic factor in the ovarian response to ovulation induction therapies.

Adult↗

[Endometriosis and fertilization in vitro. Apropos of 40 cycles].

The physiopathology and the role of endometriosis in infertility is still unclear. The use of in vitro fertilization (IVF) could be a good model for the understanding of etio-pathology and treatment when fecundity is desired. We compare results of IVF procedure in patients with endometriosis after ovulation induction with clomiphene-HMG (group 1) and Gn-Rh analog's short administration using regimen and HMG (group 2). Forty cycles have been conducted for 18 patients. Mean duration of infertility is 6.9 years and mean age of patients is 34.8 years. We observed no difference in terms of results of ovulation induction in Gr 1 or in Gr 2 compared with IVF patients without endometriosis and after the same treatment regimen, except a non significant decrease in the number of recovered oocytes. As for IVF patients without endometriosis, the use of Gn Rh analogs permits an improvement of results in terms of suppression of spontaneous premature LH surge, and increase of number of follicles and cleaved embryos. The fertilization and cleavage rates are not affected by the presence of endometriosis when compared to IVF patients without endometriosis. The number of recovered oocytes decreases with the severity of endometriosis (RAFS classification), but the pregnancy rate is not affected. Overall Third trimester pregnancy rate is 12.5% per induction cycle and 21.7% per embryo transfer. We may conclude that the presence of endometriosis does not affect the quality of the oocyte and is not a cause of exclusion in an IVF program.

Adult↗

In vitro fertilization of in vitro matured oocytes obtained from the follicles without hCG exposure for prevention of severe ovarian hyperstimulation syndrome: a case report.

We aspirated ovarian follicles of an infertile patient who encountered a great risk of ovarian hyperstimulation (OHSS) during her ovulation-induction cycle, which had been stimulated with gonadotropins, in order to avoid OHSS without interrupting the treatment. If this action were to yield a considerable number of immature oocytes, some of which were to achieve in vitro maturation and subsequent fertilization, this method could be an alternative to conventional ovulation-induction methods for patients who repeatedly present imminent signs of hyperstimulation. However, the number of oocytes collected from the patient was disappointingly low, even though a large number of follicles were thoroughly aspirated. One of these oocytes was matured in vitro in a medium containing 30% follicular fluid and granulosa cells of mature follicles, fertilized, cryopreserved, and transferred in a later artificial cycle; but pregnancy was not achieved. A low number of recovered oocytes from patients in this situation might be a factor that greatly limits the clinical applications of this method.

Adult↗

Assessment of the follicular cortisol:cortisone ratio

Cortisol and cortisone concentrations in serum and follicular fluid (FF) from women undergoing in-vitro fertilization (IVF) treatment were monitored. Four groups were included: group 1, women in their natural menstrual cycle having an endogenous mid-cycle surge of gonadotrophins; group 2, women in their natural menstrual cycle receiving human chorionic gonadotrophin (HCG) for ovulation induction; group 3, women receiving exogenous gonadotrophins for ovarian stimulation and HCG for ovulation induction; and group 4, women receiving exogenous gonadotrophins for ovarian stimulation, follicles being aspirated immediately before administration of HCG. In this study, 12 follicles contained oocytes which resulted in clinical pregnancy after IVF. Cortisone concentrations were significantly higher in FF compared with that of matched serum samples, while the opposite was observed for cortisol, resulting in cortisol:cortisone ratios being significantly lower in FF compared with serum. FF from group 4 showed significantly higher cortisone concentrations than FF from each of the other three groups. FF from group 1 showed significantly higher cortisone concentrations and significantly lower cortisol:cortisone ratios in comparison with groups 2 and 3. None of the observed parameters pinpointed any of the follicles containing oocytes which resulted in a clinical pregnancy. The intrafollicular concentrations of cortisol and cortisone suggest that pre-ovulatory follicles actively convert cortisol to cortisone. Neither FF concentrations of cortisol and cortisone nor the cortisol:cortisone ratio seem to reflect implantation potential of the derived pre-embryos.

Journal Article↗

[Association between ovarian stimulation regime and protein metabolism of patients undergoing IVF/ICSI therapy].

The aim of this study was to determine the relationship between the ovarian stimulation protocol (with HMG or FSH) after down-regulation with GnRH anologa and protein (total protein and albumin) as well as bilirubin and urea in serum. Furthermore, it was intended to find out the effect of these parameters on IVF/ICSI outcome. 50 patients were included in this study. All patients underwent controlled ovarian hyperstimulation for assisted reproduction therapy either with FSH (Gonal-F) or HMG (Menogon). Ovulation induction was induced by human chorionic gonadotrophine (HCG, Predalon) 10 000 IU i. m. The protein concentration (total protein, albumin) as well as bilirubin and urea concentrations were determined before down-regulation with GnRHa, at the beginning of ovarian stimulation with FSH or HMG, on the day of ovulation induction with HCG, during oocyte retrieval and fourteen days after embryo transfer. The age, body mass index and etiology of infertility showed no significant difference between patients stimulated with HMG or FSH. Total protein and albumin concentration decreased significantly (p=0.001) from 77.45 +/- 5.90 g/L and 47.02 +/- 3.41 g/L to 74.60 +/- 4.6 g/L and 45.04 +/- 2.39 g/L, respectively at the time of oocyte retrieval. Whereas, no significant change with bilirubin and urea concentration was observed. However, the mean concentration of total protein, albumin, bilirubin of patients who become pregnant was higher of those who did not. In conclusion, this study shows that total protein and albumin concentration in plasma decreased during the follicular phase significantly with the application of exogenous gonadotrophins and steroid hormones in comparison to the value before down-regulation. The mean value of total protein, albumin, bilirubin of patients who become pregnant was higher (but not significant) of those who did not. However, the high individual variation in the present results shows that these parameters are not useful as a predictor of IVF/ICSI outcome.

Blood Proteins↗

[Efficacy of simultaneous use of cryopreserved semen, controlled ovarian hyperstimulation and intrauterine insemination in the treatment of sterility caused by hypergonadotropic azoospermia].

The purpose of the present study is to determine the efficacy of an artificial intrauterine insemination program with frozen donor sperm and controlled ovarian hyperstimulation as an alternative therapy for infertility cause by hypergonadotropic azoospermia. Two hundred forty three insemination cycles with frozen donor sperm were analyzed. Clomiphene citrate, pure FSH, recombinant FSH or human menopausal gonadotropins were utilized for ovulation induction; human corionic gonadotropin (hCG), 10,000 IU, was administered when one or more dominant follicles with diameter > or = 16 mm were present; intrauterine insemination was performed 36 hours after the hCG injection. The pregnancy rate per cycle was 19.9%, and the cumulative pregnancy rate was 59.3%. It is concluded that intrauterine insemination with frozen donor sperm and ovulation induction is a good alternative for male factor infertility with no available treatment.

Chorionic Gonadotropin↗

Polycystic ovary disease and the risk of pregnancy-induced hypertension.

OBJECTIVE: To compare the incidence of pregnancy-induced hypertension in patients with and without polycystic ovary disease (PCOD). STUDY DESIGN: We conducted a retrospective, case-control analysis of patients who achieved singleton pregnancies with human menopausal gonadotropin (hMG) therapy. Twenty-two PCOD patients were compared to 27 infertility patients without PCOD who were pregnant after hMG therapy. Non-PCOD patients received hMG for superovulation as part of superovulation/intrauterine insemination or in vitro fertilization/embryo transfer. PCOD patients were receiving hMG for simple ovulation induction. Pregnancy-induced hypertension was defined as late pregnancy blood pressure > 140/90 mm Hg on two readings six hours apart and return to normal blood pressure by four to six weeks postpartum. RESULTS: There were no differences between PCOD and non-PCOD patients with reference to age, body mass index, parity or other pregnancy-induced hypertension risk factors (i.e., chronic hypertension, diabetes or chronic renal disease). Pregnant PCOD patients had a much higher incidence of pregnancy-induced hypertension, 31.8% (7/22), versus non-PCOD patients, who only had a pregnancy-induced hypertension incidence of 3.7% (1/27) (P = .016, OR = 12.1, 95% CI = 1.3-566.8). CONCLUSION: PCOD patients are at very high risk of pregnancy-induced hypertension when pregnant after ovulation induction.

Case-Control Studies↗

Laparoscopic treatment of heterotopic pregnancy.

The increasing frequency of pelvic inflammatory disease and use of ovulation-induction agents has resulted in a corresponding increase in the frequency of heterotopic pregnancy. In most reported cases the diagnosis was made retrospectively at the time of laparotomy. With improvements in ultrasonography and operative laparoscopy, the diagnosis can be made preoperatively and the disease treated surgically with low morbidity. In a woman who had received clomiphene citrate for ovulation induction, the diagnosis of heterotopic pregnancy was suspected preoperatively based on transvaginal ultrasonography. The patient was treated laparoscopically by partial salpingectomy, and subsequently delivered a normal infant.

Adult↗

Effects of previous ovarian surgery for endometriosis on the outcome of assisted reproduction treatment.

Endometriosis affects 2-50% of women at reproductive age. Surgery is an option for treatment, but there is no convincing evidence that it promotes a significant improvement in fertility. Also, the removal of ovarian endometrioma might lead to a reduction in the follicular reserve and response to stimulation. Therefore, the aim of this study was to evaluate the effect of previous ovarian surgery for endometriosis on the ovarian response in assisted reproduction treatment cycles and its pregnancy outcome. A total of 61 women, with primary infertility and previously having undergone ovarian surgery for endometriosis, who had received 74 IVF/intracytoplasmic sperm injection (ICSI) cycles, were studied (study group). A further 74 patients with primary infertility who underwent 77 IVF/ICSI cycles within#10; the same period of time, at the same clinic and without previous ovarian surgery or endometriosis were studied as a control group. Patients were matched for age and treatment performed. Patients </=35 years with previous ovarian surgery had fewer retrieved oocytes than the patients in the control group (P = 0.049). The number of ampoules used for ovulation induction, duration of folliculogenesis; (days), number of follicles and fertilization rate was similar in both groups. The same was observed for pregnancy rates, with 24 patients (53.3%) having had previous ovarian surgery and 27 (56.2%) in the control group becoming pregnant. Patients >35 years with previous ovarian surgery needed more ampoules for ovulation induction (P = 0.017) and had fewer follicles and oocytes than women in the control group (P = 0.001). Duration of folliculogenesis was similar in both groups, as was fertilization rate. A total of 10 patients achieved pregnancy in the study group (34.5%) and 14 (48.3%) in the control group. Although a lower pregnancy rate was observed in patients who had undergone previous ovarian surgery, this difference was not statistically significant (P = 0.424). In conclusion, ovarian surgery for the treatment of endometriosis reduces the ovarian outcome in IVF/ICSI cycles in women >35 years old, and might also decrease pregnancy rates. Therefore, for infertile patients, non-surgical treatment might be a better option to avoid reduction of the ovarian response.

Adult↗

Pregnancy induced with menotropins in a woman with polycystic ovaries, endometrial hyperplasia, and adenocarcinoma.

A 31-year-old woman is described with PCOD associated with endometrial hyperplasia and well-differentiated adenocarcinoma. Conservative treatment with ovulation induction was pursued for a total of 3 1/2 years. After CC treatment failed to achieve conception, treatment with menotropins resulted in a twin pregnancy that aborted spontaneously and a singleton term pregnancy. Hysterectomy was performed 4 1/2 years after the initial diagnosis of well-differentiated endometrial adenocarcinoma was made. Histologic examination of the endometrium showed no progression of the disease. Ovulation induction of patients with polycystic ovaries and well-differentiated and noninvasive endometrial adenocarcinoma may be justified in properly selected cases.

Adenocarcinoma↗

Human chorionic gonadotropin and relaxin concentrations in early ectopic and normal pregnancies.

The present study was performed to investigate whether determination of serum relaxin concentrations would allow assessment of the gestation further than that provided by determination of hCG. Serum relaxin concentrations were quantified in women with resorbing ectopic gestations (as documented by declining titers of beta-hCG). The control group consisted of individuals with intrauterine pregnancies. As an additional control, we studied pregnancies conceived through ovulation induction, which usually have an increased volume of relaxin-secreting luteal tissue. On days 39-70 of gestation, the mean serum relaxin concentrations were significantly lower in ten resorbing ectopic gestations (P less than .001, permutation test) than in the normal control group of 13 intrauterine pregnancies. The median serum relaxin concentrations in patients who had ovulation induction with Pergonal were substantially higher than the median for all normal controls; values in clomiphene citrate-treated patients were within the normal range. These data suggest that relaxin secretion correlates with luteal function in both normal and abnormal gestations and reflects the status of the pregnancy. Thus, relaxin may serve as a useful clinical marker.

Adolescent↗

Serum levels of insulin-like growth factor binding protein-1 and ovulatory responses to clomiphene citrate in women with polycystic ovarian disease.

OBJECTIVE: To study the serum levels of insulin, insulin-like growth factor I (IGF-I), and insulin-like growth factor binding protein-1 (IGFBP-1) in relation to clomiphene citrate (CC) responsiveness in women with polycystic ovarian disease (PCOD). DESIGN: Prospective. PATIENTS, SETTING: Twenty-three women with PCOD admitted consecutively to the University Infertility Clinic, a tertiary referral center. INTERVENTIONS: Blood samples were taken at fasting state and during oral glucose tolerance test (OGTT) for the determination of insulin, IGF-I, and IGFBP-1. A dose of 50 to 200 mg/d CC was given for ovulation induction. RESULTS: With CC treatment, ovulation was achieved in 13 of 23 PCOD patients. The IGFBP-1 concentration was lower in CC nonresponders than in CC responders (20.5 +/- 4.0 ng/mL versus 41.0 +/- 8.5 ng/mL) (P < 0.05). This difference was accentuated in 13 lean PCOD patients. Lean CC nonresponders (n = 7) had almost threefold lower serum IGFBP-1 levels than lean CC responders (n = 6) (24.0 +/- 3.1 ng/mL versus 61.8 +/- 8.6 ng/mL) (P < 0.01). By contrast, among 10 obese PCOD patients, the IGFBP-1 levels were low irrespective of CC responsiveness (14.8 +/- 8.0 ng/mL versus 16.7 +/- 7.2 ng/mL). The differences remained during OGTT. The concentrations of IGF-I, insulin, sex hormone-binding globulin, LH, FSH, and androgens showed no significant differences between CC responders and nonresponders. There was an inverse correlation between serum insulin and IGFBP-1 levels in obese PCOD patients, whereas this was not seen in lean patients. CONCLUSION: In lean PCOD patients, low serum IGFBP-1 concentration is related to CC unresponsiveness by a mechanism unrelated to insulin.

Adult↗

The etiology of ectopic pregnancy.

The cause of ectopic pregnancy is associated with two major categories: the integrity of the oviduct and the quality of the fertilized ovum. Several conditions that alter the tubal transport system include inflammatory insults, intrauterine devices, surgical manipulation, tubal ligations, salpingitis isthmica nodusa, DES exposure, and induced abortions. Risk factors that may theoretically alter ovum quality or the hormonal environment include ovulation induction, fertilization in vitro, delayed ovulation, and transperitoneal ovum migration. As we continue to investigate the fallopian tube and the fertilized ovum as unique entities, our knowledge will increase about the cause of ectopic gestations.

Abortion, Induced↗

Failure of hysteroscopic insemination of the fallopian tube in synchronized cycles.

The study consisted of a randomized, controlled trial of synchronized hysteroscopic insemination of the fallopian tube (SHIFT), in which selected infertile couples underwent hormonal delay of menstruation, ovulation induction, and insemination of a selected motile sperm population into the tubal isthmus above the utero-tubal junction. Of 40 couples recruited, only 2 became pregnant, both during a nonsynchronized control cycle. No conceptions were reported in either the 72 SHIFT or 73 non-SHIFT synchronized cycles. Hysteroscopic insemination was found to be a relatively easy procedure with a low rate of technical failure. There was low morbidity with no major clinical complications. However, 57% of tracked synchronized cycles showed a failed response to the follicular stimulation protocol; and 91% showed failure of follicular rupture greater than or equal to 52 hours after hCG induction. These failures of the ovulation synchronization/induction regimen were probably due to the use of medroxyprogesterone acetate for cycle synchronization, and should not preclude further evaluation of the technique of hysteroscopic insemination.

Clinical Trials as Topic↗