Evaluation of hormonal testing in the screening forin vitro fertilization (IVF) of women with tubal factor infertility

Purpose To evaluate the frequency of abnormal prolactin and thyroid stimulating hormone (TSH) test results in ovulatory women with tubal factor infertility who were screened for in vitrofertilization (IVF).Methods Charts were identified from 112 ovulatory women with follicle stimulating hormone (FSH) <20 mIU/ml who were diagnosed with tubal factor infertility and were screened for IVF with thyroid stimulating hormone (TSH) and prolactin levels. Women previously diagnosed with thyroid disease were subsequently excluded and 98 subjects remained. All subjects were determined to be ovulatory by biphasic basal body temperature (BBT) charts, luteal phase progesterone >4 ng/ml, or endometrial biopsy revealing secretory endometrium. Results of cycle day 3 serum TSH and prolactin concentrations were recorded. The normal range for each test reflects the geometric mean ±2 standard deviations (i.e., 95% interval), as obtained from the reference laboratory. Under this construct, hypothesis tests were performed to determine whether or not our study population was consistent with the reference range of normal hormone levels. Under the null hypothesis (normal levels), we expected 5% of the TSH tests to be abnormal (i.e., high or low levels), and 2.5% of the prolactin tests to be abnormal (i.e., high levels). Exact bionomial confidence intervals and P-values were calculated. We also tested for age trend in the proportion of abnormal results.Results Study subjects had an age range of 25–43. In the study group, 4 (0.041) out of the 98 women screened had abnormal TSH levels. Of these four abnormal TSH results, three were elevated (i.e., TSH> 4.6 IU/ml) and one was low (i.e., TSH <0.6 IU/ml). The frequency of an abnormal TSH value was not significantly different from that expected from the reference laboratory normal values (95% CI 0.011, 0.101). Of the 98 subjects, 7 (0.071) had abnormal prolactin levels, which was significantly different from that expected from the reference laboratory normal values (95% CI 0.029, 0.142;P=0.023). When stratified by age, there was no observed trend of abnormalities for TSH or prolactin levels with increasing age.Conclusions In ovulatory women presenting for IVF with tubal factor infertility, our results show that routine screening with a TSH test does not yield a significantly higher proportion of abnormal results than that expected from the reference laboratory normal values. However, prolactin level screening was found to yield a higher incidence of abnormal tests than expected from the reference laboratory normal values.Presented at the 50th Annual Meeting of the American Fertility Society, San Antonio, Texas, November 5–10, 1994.     

Superovulation before IVF by recombinant versus urinary human FSH (combined with a long GnRH analog protocol): A comparative study

Purpose Gonal-F (Serono, Aubonne, Switzerland) is a recombinant human follicle stimulating hormone (FSH) synthesized in vitroby cells into which genes encoding for FSH subunits have been inserted. This preparation exhibits physiochemical, immunological, and pharmacological properties that bear great similarity to those of native human FSH. It has a high specific activity and can be administered subcutaneously. To compare the efficacy and safety of Gonal-F with those of urinary human FSH (Metrodin; Serono) in achieving superovulation for IVF purposes in a prospective, randomized study.Methods Twenty infertile patients (normo-ovulatory healthy women) were recruited for the study and allocated at random to the Gonal-F or Metrodin groups. The treatment protocol consisted of pituitary down regulation by GnRH analog (Buserelin; Hoechst, Frankfurt, Germany) employing the long protocol initiated at the midluteal phase (900 g/day, intranasal administration). Gonal-F (SC) or Metrodin (IM) was injected daily (225 IU/day) starting on cycle day 3. Dose adjustment was performed, when necessary, from cycle day 7.Results Of the 20 cycles analyzed, none was canceled due to poor response. No cases of adverse effects (including local intolerance) or ovarian hyperstimulation syndrome were recorded in either group. They did not differ significantly in the following treatment-dependent variables: hormone profile, duration of FSH treatment, total FSH dose required to achieve follicular maturation, and the number of oocytes retrieved, fertilized, and replaced.Conclusions These preliminary data concur with previous studies in demonstrating that Gonal-F is as effective and safe as Metrodin (when given in combination with a long protocol of GnRH analog) in inducing controlled ovarian hyperstimulation for IVF purposes. Its mode of administration (SC instead of IM) offers an additional advantage over the urinary human FSH.Presented at the 50th Annual Meeting of the American Fertility Society, San Antonio, Texas, November 5–10, 1994.     

A novel oocyte maturation trigger using 1500 IU of human chorionic gonadotropin plus 450 IU of follicle-stimulating hormone may decrease ovarian hyperstimulation syndrome across all in vitro fertilization stimulation protocols

Purpose

Modification of the trigger used to induce final oocyte maturation in in vitro fertilization (IVF) is a major strategy used to reduce the risk of ovarian hyperstimulation syndrome (OHSS). A novel trigger composed of 1500 IU of human chorionic gonadotropin (hCG) plus 450 IU of follicle-stimulating hormone (FSH) has been developed to reduce OHSS risk. This study compares outcomes of the novel trigger to conventional triggers used in high-risk OHSS patients undergoing IVF.

Methods

In this retrospective cohort study, IVF cycles at high risk for OHSS based on a serum estradiol > 5000 pg/ml on trigger day conducted between January 2008 and February 2016 were evaluated. Oocyte maturation was induced with the novel trigger (1500 IU hCG plus 450 IU FSH) or a conventional trigger [3300 IU hCG, gonadotropin-releasing hormone agonist (GnRHa) alone, or GnRHa plus 1500 IU hCG]. IVF cycle outcomes were compared. Trigger strategies were examined for associations with OHSS development using logistic regression.

Results

Among 298 eligible IVF cycles identified, there were no differences in oocyte maturation, fertilization, embryo quality, or pregnancy outcomes among all triggers. After adjusting for serum estradiol level and number of follicles, the novel trigger was associated with lower odds of OHSS symptom development compared to the 3300 IU hCG and GnRHa plus hCG 1500 IU triggers (p = 0.007 and 0.04, respectively).

Conclusions

This study suggests that 1500 IU hCG plus 450 IU FSH may be associated with decreased OHSS symptoms compared to conventional triggers, while producing similar IVF and pregnancy outcomes. More important, this novel trigger may provide a superior alternative in down-regulated cycles and in patients with hypothalamic dysfunction where GnRHa triggers cannot be utilized.

     

A Randomized,Double-Blind,Multicenter Study Comparing a Starting Dose of 100 IU or 200 IU of Recombinant Follicle Stimulating Hormone (Puregon®) in Women Undergoing Controlled Ovarian Hyperstimulation for IVF Treatment

Purpose:: To compare the efficiency and efficacy of two starting doses of recombinant FSH (follitropin-, Puregon) in women undergoing IVF treatment.Methods: This prospective, randomized, double-blind, multicentric (N = 6) study included 192 women undergoing IVF using the long protocol of GnRH agonist who received either 100 IU or 200 IU of r-FSH per day. Gonadotropin dose adjustment was allowed after day 4 of stimulation.Results: The average (SD) number of oocytes retrieved was 10.9 (5.4) and 12.2 (5.6) in the 100 IU and 200 IU group respectively (p = 0.067). The total doses of Puregon administered were 1887 IU and 2559 IU in the 100 IU and 200 IU group respectively. The number of transferable embryos, and the rates of pregnancies, cancelled cycles, miscarriages and adverse events including OHSS were comparable between the two groups.Conclusions: Women undergoing IVF have similar outcomes whether recombinant FSH is commenced in a dose of 100 IU or 200 IU for the first 4 days of stimulation.     

Endogenous LH Surge Versus hCG as Ovulation Trigger After Low-Dose Highly Purified FSH in IUI: A Comparison of 761 Cycles

Purpose: The results obtained with a protocol consisting of ovarian stimulation with low doses of highly purified FSH (FSH HP), administration of a GnRH analogue to induce an endogenous surge of gonadotropins, and IUI were evaluated. These results were compared with those seen with similar FSH stimulation and hCG administration followed by IUI. Methods: Three hundred sixty-four patients scheduled for IUI, after inclusion in a total of 345 FSH HP/GnRH-stimulated cycles and 416 FSH HP/HCG-stimulated cycles, were studied. The stimulation protocol consisted of daily subcutaneous injection of 75 IU of FSH HP from day 3 or 5 of the cycle, depending on the duration of the spontaneous cycle. hCG was administered on days 0, +2, and +5 to support the luteal phase. Monitoring was conducted using circulating estradiol levels and vaginal ultrasonography. Administration of two s.c. doses of leuprolide acetate (LA) or 7500 IU of i.m. hCG when at least one 18-mm-diameter follicle was seen and estradiol levels reached 120 pg/ml per follicle with a diameter 16 mm. Intrauterine insemination was with semen capacitated by swim-up, thawed at room temperature if previously frozen. Results: The ovulation rate was 99.28 after hCG and 99.23 with LA. No significant differences were seen between the estradiol and progesterone levels of both groups or in the estradiol/progesterone ratio. The duration of the luteal phase was similar in both groups. Pregnancy rates per cycle were 17.31% (hCG) and 27.25% (LA), respectively (P = 0.0007), and abortion rates 22.22% (hCG) and 24.47% (LA), respectively. No cases of ovarian hyperstimulation were seen. Conclusions: After FSH HP administration according to a low-dose protocol, the use of LA to trigger a gonadotropin surge as a means of inducing ovulation in FSH-stimulated women could be a good alternative to improve the results and prevent ovarian hyperstimulation in IUI cycles.     

Rescue in vitro fertilization using a GnRH antagonist in hyper-responders from gonadotropin intrauterine insemination (IUI) cycles

Objective

To evaluate the outcomes in the conversion of high-response gonadotropin intrauterine insemination (IUI) cycles to “rescue” in vitro fertilization (IVF) using a Gonadotropin-Releasing Hormone (GnRH) antagonist, with regards to implantation rates, pregnancy rates, cost, and ovarian hyperstimulation syndrome (OHSS) as compared to matched, hyper-responder, IVF controls.

Methods

This prospective cohort study was conducted between January 2007 and December 2009 at our institution. In order to decrease high-order multiple pregnancy, minimize the incidence of OHSS, and avoid cycle cancellation, high-response stimulated-IUI patients opted to convert to “rescue” IVF using the GnRH antagonist cetrorelix acetate. We then compared their clinical outcomes with matched patients from high-response IVF cycles of the standard long mid-luteal GnRH agonist protocol (14 or more collected oocytes). Only cases of conventional IVF without intra-cytoplasmic sperm injection (ICSI) were included in the control group.

Results

Out of 184 patients undergoing stimulated-IUI cycles with gonadotropins, 87 patients developed a hyper-response, and 20 opted to convert to “rescue” IVF. These patients were compared with 157 matched, hyper responder IVF controls from our registry. The implantation rate was 25.6 % in the “rescue” IVF group and 20.7 % in the control IVF group (p < 0.0047). The ongoing clinical pregnancy rate per embryo transfer was 45.0 % and 33.6 % in the “rescue” IVF and the control IVF groups, respectively (p < 0.0001). The mean duration of stimulation was comparable between cohorts (10.0 vs.10.4 days, p = 0.6324). The mean dose of gonadotropin used per cycle was higher in the control group, 2664 international units (IU) of follicle stimulation hormone (FSH) compared to 1450 IU of FSH in the “rescue” IVF group (p < 0.0001). The incidence of severe OHSS is also higher in the control group, 5.1 % versus no cases in the “rescue” IVF group (p < 0.0001).

Conclusion

Our study demonstrates that conversion of high-response gonadotropin-IUI cycles to “rescue” IVF using a GnRH antagonist is a cost-effective strategy that produces better results than regular IVF with relatively minimal morbidity, and shorter duration to achieve pregnancy. Implantation and ongoing clinical pregnancy rates tend to be higher than those from hyper-responder regular IVF patients.     

The significance of elevated early follicular-phase follicle stimulating hormone (FSH) levels: Observations in unstimulated in vitro fertilization cycles

Objective: Our objective was to determine the effect of elevated early follicular-phase serum follicle stimulating hormone (FSH) levels on follicle growth and oocyte maturity in unstimulated in vitro fertilization (IVF) cycles. Study Design: We compared cycles with elevated day 3 FSH levels (>20 mIU/ml) to subsequent cycles in the same patients when day 3 FSH returned to normal and to cycles among women with normal day 3 FSH levels. Patients: Seven cycles in seven patients had an elevated day 3 FSH (high-FSH group). These were compared to 11 subsequent cycles in which there was a return to a normal baseline FSH and to 13 cycles in 13 patients that entered the unstimulated protocol with a normal baseline day 3 FSH. Results: The day of human chorionic gonadotropin (hCG) administration was similar in all groups as were the serum estradiol (E₂) levels. Although the high-FSH group tended to have smaller maximum follicular diameters, the difference was not statistically significant. The highest FSH level on cycle day 3 in a completed cycle was 56.2 mIU/ml. The total number of oocytes aspirated and the number of embryos obtained was similar in all groups. Whereas there were no pregnancies in the high-FSH group, 2 of the subsequent 11 normal day 3 FSH cycles resulted in clinical pregnancies. Two of the 13 patients in the normal day 3 FSH values also achieved pregnancies. Conclusions: We conclude that cycle day 3 serum FSH levels as high as 56.2 mIU/ml may be associated with apparently normal follicular growth, oocyte fertilization, and embryo cleavage in unstimulated cycles. However, pregnancies are not observed. In addition, FSH levels vary widely from cycle to cycle and elevated levels in one cycle do not necessarily imply that pregnancy may not occur in a subsequent cycle when FSH levels return to normal.     

Thyroid carcinoma on an ovarian teratoma: a case report and review of the literature

Metformin effectively restores insulin sensitivity in insulin-resistant women with polycystic ovary syndrome (PCOS). We examined whether metformin ,given prior to and during ovarian stimulation for in vitro fertilization (IVF) ,altered follicle stimulating hormone (FSH) requirement and increased the number of collected oocytes in these women. Seventeen insulin-resistant women with PCOS were recruited to our IVF unit to receive two consecutive cycles of ovarian stimulation with or without metformin co-treatment ,the order of treatments being randomized using a table of random numbers. Metformin treatment (1500 mg/day) started 3 weeks before downregulation with buserelin acetate and was continued throughout ovarian stimulation with human recombinant FSH. Nine women completed both cycles ,the results of eight women being excluded because of pregnancy after the first cycle (n = 4) or because the protocol of the study was not followed (n = 4). Mean total FSH dose was 2301 IU (range 1500-6563 IU) in metformin cycles and 2174 IU (range 1200-3900 IU) in parallel control cycles ,while the mean number of collected oocytes was 8.6 (range 2-28) and 4.6 (range 1-16) ,respectively. Bayesian analysis showed probabilities of 0.05 that metformin reduces FSH requirement by at least 10% ,and of 0.61 that at least 10% more oocytes are collected after metformin co-treatment. Co-administration of metformin is therefore likely to increase the number of oocytes collected after ovarian stimulation in insulin-resistant women with PCOS but is unlikely to reduce the requirement for FSH.     

Use of endotoxin as a positive (toxic) control in the mouse embryo assay

Purpose The mouse embryo assay (MEA) is used to test media used for in vitrofertilization (IVF). Negative controls usually consist of previously tested media known to support growth of embryos to the blastocyst stage by 72 h. Often, no concurrent positive (toxic) controls are reported. Thus, any unusually hardy cohort of embryos may go undetected. Endotoxin was tested for its suitability as a positive control in the MEA.Results Female mice were stimulated with gonadotropins mated with males, and embryos flushed from their oviducts 36 h after HCG injection. Two-cell embryos were pooled and randomly distributed to culture dishes containing media without protein supplement. Endotoxin inhibited blastocyst growth beginning at 50 g/ml, with complete suppression of development at 5000 g/ml. With 500 g/ml endotoxin, an average of 34.8% of the embryos developed to the blastocyst stage for eight separate assays. The interassay coefficient of variation (CV) was 76%, while the intraassay CV was 9.4%. At 48 h the zona pellucida was absent from all of the embryos exposed to the endotoxin. A large difference was found between two lots of endotoxin with the same claimed potency.Conclusions These studies demonstrate the importance for inclusion of a well-defined positive control when performing the mouse embryo assay.Presented at the 50th Annual Meeting of the American Fertility Society, San Antonio, Texas, November 5–10, 1994.     

Efficacy of low dose hCG on oocyte maturity for ovarian stimulation in poor responder women undergoing intracytoplasmic sperm injection cycle: a randomized controlled trial

Purpose

To investigate the effect of late follicular administration of low dose hCG on oocyte maturity in poor responding women undergoing intracytoplasmic sperm injection (ICSI).

Materials and methods

This prospective randomized pilot trial was performed on 73 poor responders undergoing ICSI, in Reproductive Biomedicine Research Center, Royan Institute, Tehran, Iran. All eligible patients underwent a GnRH-a long protocol and were randomly allocated into three study groups for ovarian stimulation: groupA received recombinant FSH alone, group B received recombinant FSH supplemented by 100 IU hCG. Group C received recombinant FSH supplemented by 200 IU hCG. The main endpoint was the number of metaphase II oocytes retrieved.

Results

Of 78 poor responding patients entered to this study, 73 women were considered eligible for enrolment. Of these, 26 women were allocated to receive only recombinant FSH, 24 patients allocated to receive recombinant FSH and 100 IU hCG and 23 patients were assigned to receive recombinant FSH and 200 IU hCG. Number of oocytes retrieved were significantly higher in group B compared to group A (6.5 ± 3.3 versus 4.0 ± 2.3; P = .03). Other cycle and clinical outcomes were comparable between three groups.

Conclusions

The present study demonstrated that adding 100 IU hCG to rFSH in a GnRH agonist cycle in poor responders improve response to stimulation whereas the number of metaphase II oocytes remains comparable between groups. The existence of a possible trend toward higher mature oocytes and lower total dosage rFSH in patients received 100 or 200 IU hCG is probably due to the small sample size that means further large clinical trials in a more homogenous population is required (clinical trial registration number; {"type":"clinical-trial","attrs":{"text":"NCT01509833","term_id":"NCT01509833"}}NCT01509833).     

Recurrent IVF failure is associated with elevated progesterone on the day of hCG administration

Objective

During in vitro fertilization (IVF) treatment, elevated progesterone on the day of human chorionic gonadotrophin (hCG) administration has been reported to be associated with a reduced chance of live birth. It is not known, however, if the relationship is casual or causal. In the latter situation, one would expect the incidence of elevated progesterone on the day of hCG administration to increase with the number of IVF/embryo transfer (ET) failures. The aim of this study was to investigate if the frequency of elevated progesterone on the day of hCG administration is related to the number of IVF failures.

Study design

This retrospective, observational, cohort study included a consecutive series of 6673 IVF cycles. Subjects were categorized into one of three groups: Group I, no previous IVF/ET treatment; Group II, one previous IVF/ET treatment failure; or Group III, two or more previous IVF/ET treatment failures. The main outcome measure was the proportion of cycles with elevated progesterone (>6 nmol/l) on the day of hCG administration.

Results

After adjusting for age, oestradiol level on the day of hCG administration and number of oocytes retrieved, the proportion of women with elevated progesterone on the day of hCG administration remained significantly different between the three groups: Group I, 16.8%; Group II, 31.7%; and Group III, 39.7% (p < 0.001).

Conclusion

Elevated progesterone on the day of hCG administration is more likely in women with recurrent IVF failure. Women with two or more IVF failures are twice as likely to have elevated progesterone on the day of hCG administration as women undergoing their first IVF cycle.     

A group-comparative,randomized, double-blind comparison of the efficacy and efficiency of two fixed daily dose regimens (100- and 200-IU) of recombinant follicle stimulating hormone (rFSH,Puregon) in Asian women undergoing ovarian stimulation for IVF/ICSI

Purpose : To compare the efficacy, efficacy and safety of a fixed daily dose of recombinant FSH (Puregon®) of a 100- and 200-IU regimen in Asian women undergoing ovarian stimulation for IVF/ICSI. Methods : This was a prospective, randomized, double-blind, multicenter (n = 9) study. Prior to the start of rFSH, all women were pretreated with a gonadotropin releasing hormone agonist (GnRH-a) for pituitary downregulation. Results : A total of 330 women were treated with rFSH: 163 subjects with 100 IU and 167 subjects with . In the 200 IU treatment group, significantly more oocytes were retrieved compared to the 100 IU group (9.6 vs. 5.0 oocytes, p < 0.001). The total dose rFSH needed to develop at least three follicles with a diameter of 17 mm was significantly lower in the 100 IU treatment group (1194 vs. 2034 IU, p < 0.001). Although more cycle cancellations were seen in the 100 IU group (24 vs. 13%), the ongoing pregnancy rate per started cycle was comparable between both groups (16.6% in the 100 IU group vs. 15.0% in the 200 IU group). Conclusions : The use of a 100 IU fixed dose is less effective in terms of the number of oocytes retrieved and the higher cancellation rate, but more efficient as indicated by a lower total recombinant FSH dose needed.     

MILD ovarian stimulation with GnRH-antagonist vs. long protocol with low dose FSH for non-PCO high responders undergoing IVF: a prospective, randomized study including thawing cycles

Objective

To compare the effectiveness of two stimulation protocols in non-polycystic ovary (PCO) high responders undergoing in vitro fertilization (IVF).

Design

Prospective randomized trial.

Setting

A Reproductive Medicine and IVF Unit of a University Hospital and a private IVF Clinic.

Methods

Four hundred-and-twelve normoovulatory women with good ovarian responsiveness were randomized to receive either the “mild” (FSH 150 IU/day from day 4 of a spontaneous cycle followed by GnRH-antagonist from day 8; n = 205) or the “long” (FSH 150 IU/day; n = 207) stimulation protocol. The outcome of these two regimens was compared including “fresh” and thawing cycles.

Results

The total FSH dose and the peak estradiol level were significantly lower in the “mild” protocol, whereas the retrieved oocytes, fertilization rate, number and quality of embryos, pregnancy and implantation rates, cumulative “fresh plus thaw” success rate, and incidence of severe ovarian hyperstimulation syndrome were comparable with the two regimens.

Conclusions

In young, normoovulatory patients with good ovarian responsiveness undergoing IVF the “mild” stimulation protocol has effectiveness and risks comparable to the “long” protocol with low FSH starting dose, even when thawing cycles are included in the comparison.     

Ovulation triggering in clomiphene citrate-stimulated cycles: Human chorionic gonadotropin versus a gonadotropin releasing hormone agonist

Purpose To compare the use of human chorionic gonadotropin (hCG) to a gonadotropin releasing hormone (GnRH) agonist, nafarelin, in initiating ovulation and supporting the luteal phase after priming with clomiphene.Methods In 26 infertile women 50 mg clomiphene citrate produced a preovulatory-size follicle. Then, 11 women were randomized to receive two 400-g doses of nafarelin intranasally 16 h apart, and 15 women were injected intramuscularly with 5000 IU of hCG (luteal day 0 = LD0). Starting on LD6, 7 more 400-g doses of nafarelin were repeated on an every 16-h schedule or a single 2500 IU dose of hCG was given, respectively. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂), progesterone (P), and hCG were measured. On LD13, endometrium was evaluated with ultrasonography and biopsy in 19 nonpregnant women.Results As judged by a threefold rise in serum LH, an LH surge was detected on LD1 in all 11 nafarelin patients, but in only 8 hCG patients (P = 0.01). LH and FSH levels were significantly higher on LD1, 7, and 8 and were significantly suppressed on LD13 in the nafarelin group. All patients had mid-luteal P levels greater than 10 ng/ml and luteal phases longer than 13 days. Significantly different luteal E₂ or P levels were noted only on LD13, with lower values in the nafarelin group. Pregnancies were achieved in 3 of 11 nafarelin cycles and 2 of 15 hCG cycles. Luteal phase defects were also similar: 4 of 8 nafarelin patients and 7 of 11 hCG patients.Conclusion Nafarelin or hCG in conjunction with clomiphene can result in viable pregnancies, but is associated with low pregnancy rates and a high incidence of luteal phase defects.     

The effect of oral contraceptive pill for cycle scheduling prior to GnRH-antagonist protocol on IVF cycle parameters and pregnancy outcome

Objective To evaluate the effect of oral contraceptive pills (OCP) pretreatment on IVF cycle outcome in GnRH-antagonist protocol. Design Retrospective cohort study. Setting Major tertiary university-affiliated center. Patients All patients treated with GnRH antagonist in our IVF unit during the last 3 years were included in the study. Overall 1,799 IVF cycles were performed. Of these, in 604 cycles OCP pretreatment was used prior to GnRH-antagonist for cycle scheduling. Patients were divided into two age groups—young group aged ≤35 years and older group aged ≥36 years. Interventions The young group underwent 927 cycles, 281 cycles with OCP pretreatment and 646 cycles without. The older group underwent 872 cycles, 323 cycles with OCP pretreatment and 549 cycles without. Data was analyzed within each age group. Main outcome measures Treatment duration and total dose of FSH IU used for stimulation, number of oocytes retrieved, implantation and pregnancy rates. Results All OCP-pretreated cycles required significantly longer stimulation than non-pretreated cycles (young: 10.76 vs. 9.21 days; older: 10.48 vs. 8.73 days, respectively) and higher total dose of FSH IU (young: 3,210 IU vs. 2,565 IU; older: 4,973 IU vs. 3,983 IU, respectively). There were no other differences in cycle characteristics between groups. Implantation and pregnancy rates were not affected by OCP pretreatment. Conclusions OCP pretreatment can be offered as a mode for cycle scheduling prior to GnRH-antagonist protocol, though it may be associated with longer stimulation and higher gonadotropin consumption. Capsule OCP prior to GnRH-antagonist protocol enables cycle scheduling without compromising cycle outcome and patient’s age is not a limitation in decision making for the use of this approach.     

Prediction of Pregnancy Rate of In Vitro Fertilization and Embryo Transfer in Women Aged 40 and over with Basal Uterine Artery Pulsatility Index

Purpose: The purpose was to determine the effect of basaluterine perfusion on the pregnancy rates of in vitro fertilizationand embryo transfer (IVF-ET) in women aged 40 and above. Methods: A total of 47 patient aged 40 and over underwentIVF-ET. The conception cycles and the nonconception cycleswere compared. Results: Of the 47 patients, 4 patients were pregnant (8.5%).The mean age, basal follicle stimulating hormone (FSH),basal estradiol (E₂) level, antral follicle count (AFC), numberof ampoules of gonadotropin used, E₂ levels and endometrial thickness on the day of human chorionic gonadotropin(hCG) administration, number of retrieved and fertilizedoocytes, and number of transferred embryos were not statisticallysignificant between the conception and nonconceptioncycles. However, the basal uterine artery pulsatility index(UA PI) was significantly lower in the conception cycles(P < 0.001). The receiver operating characteristics (ROC)curve analysis for basal FSH, AFC, and basal UA PI inpredicting the pregnancy rate of IVF in patients aged 40were demonstrated. The best prediction rate was achievedby a pulsatility index cutoff of < 2.0 for a receptive uterus. Conclusions: Increased uterine perfusion in the early follicularphase enhanced the pregnancy rate of IVF in womenaged 40 and above. It is therefore essential that patientsaged 40 with poor basal uterine perfusion should beidentified early in the early follicular phase of the menstrualcycle to apply appropriate intervention to improve the uterinecirculation for the subsequent chance of pregnancy.     

The effect of medical versus surgical treatment of spontaneous miscarriage on subsequent in vitro fertilization cycles

Objective: To evaluate the effect of dilation and curettage (D&C) and misoprostol as treatments for spontaneous miscarriage (SM) on in vitro fertilization (IVF) parameters in the subsequent IVF cycle.

Design: Multicenter, retrospective, cohort study. Women treated for SM after IVF treatment with D&C or misoprostol and underwent a subsequent IVF cycle was included. The main outcome measures were ovarian response, endometrial thickness and pregnancy rate in the subsequent IVF cycle after MA.

Results: Among 73 patients with miscarriage, 41 had D&C and 32 were given misoprostol. Baseline serum follicle stimulating hormone (FSH) levels and ovarian responses before and after treatment of miscarriage were comparable. No significant differences were observed between the D&C and the misoprostol groups in basal FSH levels, endometrial thickness and parameters of ovarian response in the subsequent IVF cycle.

Conclusion: D&C and misoprostol are both effective treatments for IVF patients with miscarriage, without an adverse effect on subsequent IVF treatment outcome.     

A fixed stimulation protocol for in vitro fertilization (IVF) without determinations of hormones in blood

A new fixed schedule of ovarian stimulation for IVF was developed, which is not only simpler and easier to handle for the patients but also yields better fertilization and pregnancy rates. The period and beginning of stimulation are shifted by means of a contraceptive pill, so that stimulation can generally be started on a Sunday. The patient takes 100 mg clomiphene for 5 days and 7.5 mg prednisolone for 30 days to suppress possible exaggerated adrenal androgens; she also receives 150 IU of human menopausal gonadotropin (HMG) i.m. every other day from her family physician. From the 8th day of stimulation onwards, follicular growth is registered by daily ultrasound at the IVF center. When the dominant follicle exceeds 18 mm in diameter, 5000 IU human chorionic gonadotrophin (hCG) is given. Blood sampling for hormone estimations is not necessary, and only one sample of urine is needed for the LH estimation before hCG. In comparison to clomiphene citrate (Clomid) alone, Clomid plus HMG/FSH and HMG/FSH alone, this protocol resulted in significantly higher fertilization and pregnancy rates per follicular puncture. The rate of abortions and extrauterine pregnancies, on the other hand decreased. When comparing repetitive IVF cycles with the first IVF cycle, a significant reduction of oocytes in repetitions was found, but no difference was found in the number of fertilized eggs. The pregnancy rate, on the other hand, increased in the repeat cycles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic changes induced by urinary human chorionic gonadotropin and recombinant luteinizing hormone used for inducing final follicular maturation and luteinization

OBJECTIVE: To compare the safety of recombinant human luteinizing hormone (LH) with that of urinary hCG in terms of the hemodynamic changes when they are used to induce final follicular maturation in patients undergoing in vitro fertilization (IVF). A secondary end point was efficacy in terms of IVF outcome. DESIGN: Prospective, randomized clinical trial. SETTING: University teaching hospital. PATIENT(S): Thirty IVF patients. INTERVENTION(S): Ovarian stimulation was induced with FSH under pituitary suppression. Patients were randomized to receive either hCG or recombinant human LH as a trigger of oocyte maturation (5,000 IU) and for luteal phase support (5,000 IU, 2,500 IU, and 2,500 IU on the day of follicular aspiration, 2 days later, and 5 days later, respectively). MAIN OUTCOME MEASURE(S): Mean arterial pressure, cardiac output, peripheral vascular resistance, and serum levels of progesterone, plasma concentrations of aldosterone, norepinephrine, and plasma renin activity were measured in all patients on postovulatory day 7 of the spontaneous menstrual cycle preceding IVF (baseline) and 7 days after the hCG/recombinant human LH ovulatory injection during the IVF cycle. RESULT(S): Ovarian response and IVF outcome (pregnancy rate, 60%) were similar in both treatment groups. On the seventh day after hCG/recombinant human LH administration, the peripheral vascular resistance was significantly lower and serum progesterone concentrations significantly higher in the hCG group as compared with the recombinant human LH group. The percentage change from baseline values during IVF cycles in all hemodynamic and neurohormonal variables investigated was higher (albeit not statistically different) in the group treated with hCG vs. the group treated with recombinant human LH. CONCLUSION(S): Recombinant human LH is associated with less intense circulatory changes than hCG when it is given to induce final follicular maturation and luteal phase support in IVF procedures.     

Melatonin concentration in follicular fluid is correlated with antral follicle count (AFC) and in vitro fertilization (IVF) outcomes in women undergoing assisted reproductive technology (ART) procedures

The aim of the present study was to evaluate the possible relationship between melatonin levels in the follicular fluid (FF) and in vitro fertilization (IVF) outcomes in women undergoing assisted reproductive treatment. Sixty-three females (20 to 40?years old) scheduled for IVF were divided into three groups based on their antral follicle count (AFC). We determined FF melatonin concentrations in group A (AFC≦6, n?=?21), group B (7≦AFC≦14, n?=?22), group C (AFC≧15, n?=?20) on oocyte retrieval day. Patients in group C had significantly higher melatonin levels as compared to patients in groups A and B (p?p?p?=.001), serum estradiol (E₂) levels on human chorionic gonadotropin (HCG) administration day (p?=?.001), total follicle-stimulating hormone (FSH) dose (p?=?.002), starting FSH dose (p?=?.035), number of retrieved oocytes (p?p?p?p?p?=?.004), blastocysts obtained (p?=?.007) and total embryos obtained (day3 embryos?+?day5/6 blastocysts) (p?=?.005). The levels were significantly negatively correlated with age (p?p?=?.003), serum FSH (p?=?.001) and serum luteinizing hormone (LH) levels (p?=?.003) on HCG administration day. This is the first demonstration of a significant positive correlation of melatonin concentrations with AFC in patients undergoing IVF. We propose that FF melatonin levels may influence the IVF outcomes.