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.     

Studies on the influence of gonadotrophin levels in the early follicular phase on the ovarian response to stimulation

The gonadotrophic regulation of folliculogenesis has been extensively investigated but little attention has been paid to the influence of early follicular phase levels of endogenous FSH and the FSH/LH ratio when planning ovulation stimulation therapy for IVF. The influence of these factors was investigated in the three studies reported in this paper. A fixed schedule of ovulation stimulation therapy which employed standard treatment regimens, irrespective of the ovarian response, was used to eliminate variation due to treatment factors. Cycles were pretreated with an oestrogen-progestogen contraceptive pill or a progestogen (norethisterone). It was found that both oestrogen-progestogen and progestogen alone decreased the plasma FSH level, although the FSH/LH ratio was significantly reduced only by oestrogen-progestogens. In clinical IVF studies, oestrogen-progestogen pretreatment was associated with a significant reduction in the preovulatory concentration of oestradiol in plasma and the number of aspirated follicles, compared to norethisterone. The administration of FSH for 2 days following oestrogen-progestogen pretreatment and prior to the fixed schedule of ovulation stimulation normalized ovarian steroidogenesis and follicular development. Early follicular phase supplementation with FSH had no influence on progestogen pretreated cycles. The final experiment investigated the influence of FSH/LH levels in the early follicular phase on the outcome of ovarian stimulation. The preovulatory oestradiol concentration was reduced when baseline FSH/LH levels were low compared with when these values were high. Administration of FSH for 2 days in the early follicular phase improved the preovulatory level of oestradiol when baseline FSH/LH was low but had no effect when baseline FSH/LH levels were high.(ABSTRACT TRUNCATED AT 250 WORDS)     

Poor responders to ovulation induction: is proceeding to in-vitro fertilization worthwhile?

A 'poor response' in the context of in-vitro fertilization (IVF) can be defined as failure to produce an adequate number of mature follicles, and/or a peak oestradiol concentration less than a defined minimum. The cut-off points implied in this definition vary between different centres. Many opt to cancel the IVF cycle when their defined minimum concentrations are not reached despite the lack of evidence of improved outcome in subsequent cycles. Patients attending the Oxford Fertility Unit who are 'poor responders' have always been given the option of continuing with treatment. The first cycles of IVF in 124 patients, with normal day 3 follicle stimulating hormone (FSH), who produced less than five follicles within a 2 year period were studied. The patients were divided into three groups according to the number of follicles produced: A (one or two follicles; n = 33), B (three follicles; n = 33) and C (four follicles; n = 58). The three groups were similar in age, day 3 FSH, total gonadotrophin dose, duration of stimulation, peak oestradiol concentration, oocyte yield, fertilization rate and the clinical pregnancy rate. However, group A had a significantly higher oestradiol concentration per follicle (P < 0.001). The clinical pregnancy rate/cycle in the three groups was comparable to our overall rate in the study period (25.5%). This paper suggests that poor responders with a normal day 3 FSH may still achieve a pregnancy rate similar to that of normal responders.     

Effects of gonadotrophin-releasing hormone agonists on human ovarian steroid secretion in vivo and in vitro-results of a prospective, randomized in-vitro fertilization study

The aim of this prospective randomized study was to compare the effects of two gonadotrophin-releasing hormone (GnRH) agonists, buserelin and triptorelin, on human ovarian follicular steroidogenesis, oocyte fertilization and IVF treatment outcome. Ovulatory, healthy women undergoing IVF were treated either with human menopausal gonadotrophin (HMG) alone or with HMG and one of the two GnRH agonists. Serum and follicular fluid hormonal concentrations and cultures of luteinizing granulosa cells obtained during follicular aspiration were analysed. GnRH agonist treatment significantly affected steroidogenesis both in serum and follicular fluid. In follicular fluid, progesterone and oestradiol concentrations were significantly elevated while testosterone concentrations were significantly lower in the triptorelin group. The ratios of testosterone/progesterone, oestradiol/progesterone but not oestradiol/testosterone concentrations were significantly affected by GnRH agonist administration. Similarly, the steroidogenic activity of luteinizing granulosa cells in vitro was significantly decreased in women treated with GnRH agonists. Women treated with GnRH agonists had significantly more fertilized oocytes and cleaving embryos. The results indicate a marked effect of GnRH agonists on the pattern of ovarian follicular steroidogenesis that cannot be explained solely by changes in gonadotrophin concentrations.     

Extremes of body mass do not adversely affect the outcome of superovulation and in-vitro fertilization

The effect of extremes of body mass on ovulation is well recognized by clinicians. However, the effect of obesity and extreme underweight on the outcome of in-vitro fertilization (IVF) cycles has received relatively little attention. In a retrospective nested case-control study we examined the effect of the extremes of body mass index (BMI) on IVF-embryo transfer outcome at a university-based IVF unit. A total of 333 patients were included in the study; 76 obese patients (BMI > 27.9) with 152 controls, and 35 underweight patients (BMI < 19) with 70 controls. The patients were matched with their controls in age +/- 1 year, day 3 follicle stimulating hormone (FSH) concentration, daily dose of gonadotrophin (+/- 37.25 IU), gonadotrophin preparation and the year of treatment. The following parameters were compared between the study and control groups: duration of administration and dose of gonadotrophin, number of follicles aspirated, number of eggs, fertilization rate, number of embryos, serum oestradiol concentration on human chorionic gonadotrophin (HCG) day (peak oestradiol), clinical pregnancy rate, implantation rate, miscarriage rate, and incidence of ovarian hyperstimulation syndrome. Apart from a significantly lower peak oestradiol concentration (P = 0.009) in the obese patients, they and the underweight patients were not significantly different from their normal controls. The extremes of body mass index do not adversely affect the outcome of IVF-embryo transfer treatment. However, the obese patients had lower peak oestradiol concentrations than their normal controls despite receiving similar gonadotrophin doses.     

Dynamic assays of inhibin B and oestradiol following buserelin acetate administration as predictors of ovarian response in IVF

The study was designed to examine whether dynamic measurements of inhibin B and oestradiol following single administration of buserelin acetate were correlated with the ovarian response to stimulation in IVF. A total of 37 patients undergoing IVF treatment was studied when the long protocol was started in the early follicular phase. Blood samples were taken twice: on day 2 of the menstrual cycle, before the first s.c. administration of buserelin acetate 0.5 mg and on day 3, 24 h later. Inhibin B and oestradiol concentrations were compared with the ovarian response to stimulation. The ovarian response was defined in two ways: 'number of oocytes/total recombinant (r) follicle stimulating hormone (FSH) dose'; and 'square-root (number of follicles/total rFSH dose)'. The following measurements were highly correlated with the ovarian response to stimulation: increase in oestradiol (day 3-day 2 oestradiol concentration) [correlation coefficient (r) = 0.68, P: < 0.0001] and sum of inhibin B (day 2 + day 3 inhibin B concentrations) (r = 0.6, P: < 0.0001). Age and basal concentrations of FSH and inhibin B were inferior to the above measurements in terms of correlation with the ovarian response. In conclusion, dynamic measurements of inhibin B and oestradiol following single administration of buserelin acetate were highly correlated with the ovarian response to stimulation for IVF treatment.     

Leptin during assisted reproductive cycles: the effect of ovarian stimulation and of very early pregnancy

Leptin may have a role in human reproduction. The impact of IVF and of very early pregnancy on serum leptin concentrations was studied in 66 infertile patients, of whom 19 became pregnant. Ovarian suppression was accompanied by a fall in leptin concentrations (21 +/- 4%, mean +/- SE; P < 0.01) from the mid-luteal phase, and ovarian stimulation by a rise (76 +/- 8%; P < 0.0001) from suppression. The mid-luteal concentration of leptin after stimulation was 28 +/- 7% higher than that during the preceding normal cycle (P < 0.001). Concentrations of leptin and oestradiol were related before treatment, at ovarian suppression and at 8 days after oocyte retrieval. In addition, the rises in leptin and oestradiol concentrations during stimulation were correlated, but only in those patients who became pregnant (r = 0.69; P = 0.001). Women with a successful pregnancy had higher concentrations of leptin (18.7 +/- 4.8 microg/l) at 12 days after embryo transfer than those who had miscarriages (10.0 +/- 1.9 microg/l; P < 0.001), or those failing to become pregnant (11.6 +/- 1.2 microg/l; P < 0.0001). We concluded that leptin concentrations are influenced by ovarian function and that the relationship between leptin and oestrogen (but not a single leptin concentration), may be an important factor for the outcome of IVF.     

Does ovarian stimulation for in-vitro fertilization induce a hypercoagulable state?

Effects on blood coagulation and fibrinolytic activity during ovarian stimulation for in-vitro fertilization (IVF) were examined in 12 women. Blood samples were taken prior to hormonal stimulation (days 2-3 of the menstrual cycle, mean serum oestradiol concentration 0.16 nmol/l) and the day after ovulation induction with human chorionic gonadotrophin (HCG) (days 10-12, mean serum oestradiol concentration 5.35 nmol/l). We measured whole blood clotting time, whole blood clot lysis time, plasma fibrinogen, factor VII and antithrombin III. The whole blood clotting time was slightly, but not significantly shortened after ovarian stimulation. A significant rise in plasma fibrinogen (P less than 0.001) and reduction in antithrombin III (P less than 0.001) were observed, whereas no change in factor VII was found. The blood fibrinolytic activity was significantly reduced as evaluated by an increase in the clot lysis time (P less than 0.02). These results indicate that ovarian stimulation for IVF may create a state of hypercoagulability.     

High serum oestradiol concentrations in fresh IVF cycles do not impair implantation and pregnancy rates in subsequent frozen-thawed embryo transfer cycles

High oestradiol concentrations may be detrimental to the success of in-vitro fertilization (IVF) treatment. A total of 1122 women aged <40 years who were undergoing their first IVF cycle were evaluated retrospectively. Serum oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration were categorized into three groups: group A <10 000 pmol/l; group B 10 000-20 000 pmol/l and group C >20 000 pmol/l. In fresh cycles, group A had significantly lower pregnancy rates per transfer (16.2 versus 23.7% respectively, P = 0.005, chi(2)) and implantation rates (8.7 versus 11.7% respectively, P = 0.037, chi(2)), when compared with group B. The pregnancy rate per transfer in group C was significantly lower than that in group B (12.1 versus 23.7%, P = 0.049, chi(2)) and group C had the lowest implantation rate (6.4%). In frozen-thawed embryo transfer cycles, implantation rates in groups A, B and C were similar (7.5, 8.1 and 9.6% respectively) and the pregnancy rates were also comparable in all groups. In conclusion, high serum oestradiol concentrations in fresh IVF cycles may adversely affect implantation and pregnancy rates. Embryo quality seemed unaffected as excess embryos from different groups had similar implantation and pregnancy rates in frozen-thawed embryo transfer cycles. The reduced implantation was probably due to an adverse endometrial environment resulting from high serum oestradiol concentrations.     

Ovarian response to repeated controlled stimulation in in-vitro fertilization cycles in patients with ovarian endometriosis

In-vitro fertilization (IVF) is an effective infertility treatment for women with endometriosis, but most women need to undergo several cycles of treatment to become pregnant. This case-control study was designed to assess how consistently women with ovarian endometriosis respond to ovarian stimulation in consecutive treatment cycles compared to women with tubal infertility. We compared outcome measures in 40 women with a history of surgically confirmed ovarian endometriosis and 80 women with tubal infertility, all of whom had at least three IVF treatment cycles. The groups were matched for age and early follicular follicle stimulating hormone (FSH) concentration at their first IVF cycle. Outcome measures included number of follicles, number of oocytes, peak oestradiol concentration and number of FSH ampoules required per follicle. Cumulative pregnancy and live birth rates were calculated in both groups. The ovarian endometriosis group had a significantly poorer ovarian response and required significantly more ampoules of FSH per cycle, a difference that became greater with each subsequent cycle. However, cumulative pregnancy (63.3 versus 62.6% by fifth cycle) and live birth (46.8 versus 50.9% by fifth cycle) rates were similar in both groups. In conclusion, despite decreased ovarian response to FSH, ovarian endometriosis does not decrease the chances of successful IVF treatment.     

Endocrinology: Predictive value of serum oestradiol concentrations and oocyte number in severe ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is a serious complicationof gonadotrophin usage but it is difficult to accurately predictits occurrence. Previous investigators have identified the combinationof high oestradiol concentrations and oocyte number as beingpredictive in 80% of cases. In this study we sought to identifythe incidence of severe OHSS in patients with high oestradiolconcentrations and large numbers of oocytes and to evaluatethe importance of pregnancy in the development of OHSS. Between1990 and 1993, we studied 139 cycles using two assisted reproductivetechniques [oocyte donor, n =72; in-vitro fertilization (IVF),n = 67] in which either oestradiol (>4000 pg/ml), oocytenumber (>25), or both were elevated. OHSS was diagnosed bystandard criteria. There were no cases of severe OHSS in theoocyte donor group and six in the IVF group. Among 10 patientswith oestradiol concentration >6000 pg/ml and >30 oocytes,only one had OHSS (10%). The relative risk of OHSS with pregnancywas 12 (confidence interval 2.18–66.14). We conclude thatthe risk of OHSS even at high levels of stimulation is lowerthan previously believed. Secondly, donors have a very low riskof OHSS, probably because of the absence of pregnancy. As such,cryopreservation of all oocytes in IVF cycles is a reasonablealternative to cycle cancellation or use of adjunctive medication.     

Clinical and endocrinological changes in women following ovulation induction using buserelin acetate/human menopausal gonadotrophin augmented with biosynthetic human growth hormone.

Biosynthetic human growth hormone added to an ovarian stimulation regime of human menopausal gonadotrophin (HMG) for IVF treatment improves the response of women who were previously resistant. This study investigated the efficacy of growth hormone (GH)/buserelin/HMG treatment in women with a previous normal response to buserelin/HMG stimulation. Ten patients (28-36 years, mean 32.5 years) were treated with GH (6 IU/day) plus buserelin/HMG. A control group of 10 women (28-37 years mean 31.0 years) received buserelin/HMG alone. All were given buserelin 500 micrograms and 2 ampoules (150 IU) HMG daily once pituitary suppression had been confirmed. There was no improvement in the GH group as assessed by follicular growth rate or number, oocyte number per woman and pregnancy rate. There was no effect of GH upon the serum oestradiol level and the follicular fluid levels of oestradiol, GH and inhibin. Serum IGF-1 increased significantly during GH administration, returning to pre-treatment levels 2 days after the last dose of GH. Follicular IGF-1 was much higher in the GH-treated group than the controls. Significant correlations were found in the GH-treated group between follicular fluid GH and follicular fluid oestradiol concentrations and between follicular GH and follicular size. Follicular IGF-1 was correlated with the serum IGF-1 concentration on day 8 of the GH/HMG treatment. In conclusion GH/buserelin/HMG treatment in women with a previous normal response to buserelin/HMG stimulation increased their serum and follicular IGF-1 concentrations. However, it does not improve the clinical ovarian response or the follicular secretion of oestradiol or inhibin.     

A rapid decline in serum oestradiol concentrations around the mid-luteal phase had no adverse effect on outcome in 763 assisted reproduction cycles

Progesterone is essential in the luteal phase whereas luteal oestradiol may play only a permissive role on the endometrium. However, a rapid decline in oestradiol concentrations around the mid-luteal period may compromise the endometrial integrity leading to poor IVF outcomes. A retrospective analysis of 763 women aged <40 years undergoing their first IVF cycle and having < or =3 embryos replaced was undertaken. In cycles receiving human chorionic gonadotrophin (HCG) for luteal support, 25th, 50th and 75th centiles of the ratio of day-of-HCG oestradiol to mid-luteal oestradiol (oestradiol ratio) were 1.8, 2.8 and 5.0 respectively. Hormonal parameters were not different between pregnant and non-pregnant cycles. The outcomes were similar irrespective of the oestradiol ratio. Progesterone supplementation was used instead when the HCG oestradiol was >18 000 pmol/l or there were features of ovarian hyperstimulation syndrome. Pregnancy rates of these hyperstimulated cycles were 16.7 and 11.4% per cycle respectively when oestradiol ratio was < or =5.0 and >5.0. This difference did not reach statistical significance. Our results could not find an adverse outcome in cycles showing a rapid decline in oestradiol during the mid-luteal phase.     

Ovarian stromal blood flow in the prediction of ovarian response during in vitro fertilization treatment

BACKGROUND: This study evaluated the role of ovarian stromal blood flow in the prediction of the ovarian response of infertile women by comparing age of women, body mass index (BMI), basal FSH concentration, antral follicle count (AFC) and ovarian stromal blood flow indices measured by power Doppler in two-dimensional ultrasound. Patients were aged <40 years with basal FSH <10 IU/l on recruitment for IVF treatment. METHODS: All received a standard regimen of ovarian stimulation in their first IVF cycle. AFC, pulsatility index, resistance index and peak systolic blood flow velocity of ovarian stromal vessels were determined on the second day of the treatment cycle prior to ovarian stimulation. Ovarian response was represented by the number of oocytes, serum oestradiol, and the duration and dosage of gonadotrophins. RESULTS: A total of 136 women were included in the analysis. Basal FSH concentration achieved the best predictive value in relation to the number of oocytes obtained, followed by AFC and BMI. AFC was the only predictive factor of serum oestradiol concentration on the day of HCG while BMI was predictive of the gonadotrophin dosage. CONCLUSION: Ovarian stromal blood flow indices measured by power Doppler ultrasound had no predictive value for the ovarian response.     

Is there a difference in the function of granulosa-luteal cells in patients undergoing in-vitro fertilization either with gonadotrophin-releasing hormone agonist or gonadotrophin-releasing hormone antagonist?

Gonadotrophin-releasing hormone (GnRH) regulates gonadotrophin release. It has been shown that GnRH may have a direct effect on the ovary, as the addition of GnRH to granulosa cell cultures inhibits the production of progesterone and oestradiol. Specific GnRH receptors have been found to be present in rat and human granulosa cells. Desensitization of the pituitary by GnRH agonist has become common in in-vitro fertilization (IVF) treatment, usually by a long protocol of 2-3 weeks. With the introduction of GnRH antagonists, which produce an immediate blockage of the GnRH receptors, a much shorter exposure is needed of 3-6 days. The aim of this study was to evaluate the effect of a GnRH agonist (buserelin) and a GnRH antagonist (cetrorelix) on the function of granulosa cells cultured in vitro from IVF patients. Women were treated by IVF randomized either to have buserelin nasal spray from the luteal phase in the previous cycle or cetrorelix from day 6 of the cycle. Both groups had ovarian stimulation with human menopausal gonadotrophin (HMG) 150 IU daily, i.e. HCG was administered when the follicles were larger than 17 mm, and aspirated 36 h later. Granulosa cells, separated and washed from large follicles containing ova, were pooled. After 48 h of pre-incubation, the granulosa cells were cultured for 4 days in medium with either added testosterone or cAMP with or without HCG, with change of medium after 2 days. The progesterone and oestradiol concentrations in the culture medium were measured by immunological assay, and cellular protein was measured by microprotein assay. The results showed that granulosa cells from women treated with GnRH antagonist (cetrorelix) responded earlier to the in-vitro hormone stimulation in terms of progesterone accumulation than women treated with the GnRH agonist (buserelin). This may have been due to difference in time of exposure to the analogue. The results may indicate that the luteal function is less impaired in GnRH antagonist treatment than in GnRH agonist treatment.     

Endometrial oestrogen and progesterone receptors and their relationship to sonographic appearance of the endometrium

The rapid development of ultrasonographic equipment now permits instantaneous assessment of follicles and endometrium. The sonographic appearance of the endometrium has been discussed in relation to in-vitro fertilization (IVF) cycles. However, a generally agreed view of the relationship of the sonographic appearance to fecundity in IVF cycles has not emerged. We have studied the relationship between steroid receptors and the sonographic appearance of the preovulatory endometrium in natural cycles and ovulation induction cycles. Preovulatory endometrial thickness was not found to be indicative of fecundity, although a preovulatory endometrial thickness of <9 mm related to an elevated miscarriage rate. The preovulatory endometrial echo pattern did not predict fecundity. No relationships were found among endometrial appearance, endometrial steroid receptors and steroid hormone concentrations in serum. Oestrogen or progesterone receptor concentrations were not related to endometrial thickness or to concentrations of serum oestradiol, the only significant correlation being found between the endometrial concentrations of oestrogen and progesterone receptors. The ratio of progesterone:oestrogen receptor concentration was somewhat less in echo pattern B (not triple line) endometrium compared with pattern A (triple line) endometrium. Oestrogen and progesterone receptor concentrations appeared stable on gonadotrophin induction, though fewer numbers were found during clomiphene cycles than in natural cycles. With regard to the distribution of receptor concentration between clomiphene and natural cycles, most women using clomiphene had very low oestrogen receptor populations. Pregnancy rates were low, in spite of high ovulatory rates during clomiphene treatment and were mainly related to low oestrogen receptor concentrations in preovulatory endometrium.     

A moderately elevated day 3 FSH concentration has limited predictive value, especially in younger women.

BACKGROUND: A cycle day 3 FSH concentration is a popular screening tool for predicting success in achieving pregnancy after IVF. Difficulties interpreting this test have resulted from lack of consensus in defining an elevated FSH concentration, a change in the assays, and lack of controlling for factors which may confound the association between FSH concentration and pregnancy. METHODS: Assessment was made of the ability of a moderately elevated (10-11.4 mIU/ml, World Health Organization 2nd International Standard (IRP 78/549) and elevated FSH (>11.4 mIU/ml, conversion factor to SI units, 1.00) in predicting ability to achieve pregnancy through IVF and embryo transfer, both independently, and after controlling for confounding variables such as age, diagnosis, and response to gonadotrophins. RESULTS: A total of 293 IVF cycles were retrospectively reviewed. An FSH (>11.4) was strongly associated with inability to achieve pregnancy after IVF both independently (P < 0.01) and after multivariate analysis (P < 0.01), and had a strong predictive value (100%). A moderately elevated FSH (10-11.4) was not statistically associated with pregnancy outcome either independently or after multivariate analysis, and had a low predictive value (71%). CONCLUSIONS: Much of the predictive value of an elevated FSH is confounded by poor response to gonadotrophin stimulation, which may be overcome in younger women.     

The Relationship Between Hypogammaglobulinemia,Monoclonal Gammopathy of Undetermined Significance and Humoral Immunodeficiency: a Case Series

Hypogammaglobulinemia of the non-monoclonal immunoglobulin heavy chain classes has been reported in monoclonal gammopathy of undetermined significance (MGUS) patients. Whether low polyclonal immunoglobulin levels are associated with impaired specific antibody production and whether they represent a risk factor for the development of recurrent bacterial infections have not been established in this population. We determined the frequency of MGUS in patients referred to a tertiary care clinical immunology ambulatory care practice for evaluation of hypogammaglobulinemia, who were assessed for deficits in specific antibody production and the presence of recurrent infections. Of the 133 patients evaluated for hypogammaglobulinemia, 68 were screened for monoclonal gammopathy and 5 were found to have MGUS. Three had MGUS associated hypogammaglobulinemia in the absence of a defining primary immunodeficiency, one possibly had common variable immunodeficiency, and one had an uncertain diagnosis. Thus, MGUS may be uncovered in patients presenting with hypogammaglobulinemia even in those who lack an elevated serum level of IgG, IgM, or IgA.     

The value of basal serum follicle stimulating hormone, luteinizing hormone and oestradiol concentrations following pituitary down-regulation in predicting ovarian response to stimulation with highly purified follicle stimulating hormone.

The value of gonadotrophin and oestradiol concentrations following pituitary down-regulation with leuprolide acetate in predicting ovarian response to stimulation was evaluated in three groups of women undergoing ovarian stimulation for in-vitro fertilization with highly purified follicle stimulating hormone (FSH). Leuprolide acetate was started in the midluteal phase, and either stopped at menses (IVF-SL group, n = 3), or continued throughout stimulation (IVF-LL group, n = 38; oocyte donors, n = 58). Ovarian stimulation was started on cycle day 3, after blood was drawn for down-regulated FSH, luteinizing hormone (LH) and oestradiol. Higher down-regulated LH was predictive of higher oestradiol on day 5 of stimulation in both IVF groups, and of need for fewer ampoules in the IVF-LL group, but not of oestradiol on day of human chorionic gonadotrophin (HCG) administration or number of oocytes retrieved. Higher FSH after down-regulation predicted yield of fewer oocytes in the donor and IVF-LL groups, and higher oestradiol on day 5 of stimulation, need for fewer ampoules and a shorter duration of therapy in both IVF groups. Higher oestradiol after down-regulation was associated with higher oestradiol on day 5 of stimulation and on day of HCG administration, a shorter duration of therapy and need for fewer ampoules in all groups. Whereas these results do not ascribe any predictive significance to LH, they suggest that oestradiol and FSH concentrations after down-regulation are predictive of the pattern of ovarian response to stimulation and of oocyte yield.     

In-vitro fertilization and the ovarian hyperstimulation syndrome.

Eight patients who developed severe ovarian hyperstimulation syndrome (OHSS) were identified among 1302 patients undergoing in-vitro fertilization (IVF) over a 1 year period (prevalence of 0.6%); 63% had ultrasonically diagnosed polycystic ovaries (PCO) and 75% were undergoing their first attempt at IVF. Pretreatment with a superactive luteinizing hormone-releasing hormone (LHRH) analogue significantly increased the prevalence of severe OHSS (1.1% versus 0.2%, P less than 0.05) compared with ovarian stimulation with clomiphene citrate and human menopausal gonadotrophin (HMG). The mean serum oestradiol concentration on the day of human chorionic gonadotrophin (HCG) administration was 8200 +/- 2300 pmol/l. A mean of 19.6 +/- 6.8 follicles had been aspirated and 13.1 +/- 7.7 oocytes recovered at transvaginal ultrasound-directed oocyte recovery. All patients had an embryo transfer and luteal support in the form of HCG. The clinical pregnancy rate was 88%, multiple pregnancy rate 71% and implantation rate 63.5 +/- 41.3%. In a group of seven patients who were hospitalized for moderate OHSS during the same period, peak oestradiol levels were significantly lower than in those with severe OHSS (P less than 0.05). Of the group with moderate OHSS, 57% had PCO, the clinical pregnancy rate was 100% and multiple pregnancy rate 43%. Patients with ultrasound-diagnosed PCO have an increased risk of developing OHSS and the dose of HMG administered to them should be minimized. In patients at risk of developing OHSS, progesterone instead of HCG should be used for luteal support. Transfer of a maximum of two embryos or freezing all embryos for transfer in a subsequent cycle may reduce the likelihood of multiple pregnancy.