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.     

Endocrinology: Progesterone alone versus progesterone combined with HCG as luteal support in GnRHa/HMG induced IVF cycles: a randomized clinical trial

Two different regimens of luteal support in gonadotrophin hormone-releasinghormone (GnRH) analoguefhuman menopausal gonadotrophin (GnRHa/HMG)-inducedin-vitro fertilization cycles (IVF) were compared in a randomizedclinical trial. After embryo transfer, either vaginal progesteronealone was administered (n=89, P group), or a combination ofvaginal progesterone and human chorionic gonadotrophin (n=87,P/HCG group). The primary aim of this study was to assess theeffect of the different regimens of luteal support on the pregnancyrate. The secondary aim was to compare oestradiol and progesteroneconcentrations in the luteal phase between the two groups, andassess their effect on the pregnancy rate. A clinical pregnancyrate of 15% was found in the P/HCG group in comparison with26% in the P group (odds ratio 0.49; 99% confidence interval:0.18–1.3). The luteal serum oestradiol and progesteronevalues in the P/HCG group were significantly higher when comparedwith the P group on the 6th, 9th and 12th day after oocyte retrieval(Wilcoxon P<0.001). In accordance with the high oestradiolconcentrations, more cases of ovarian hyperstimulation syndrome(OHSS) were found in the P/HCG group. Oestradiol values on the9th day after oocyte retrieval, presumably the day of implantation,appeared to be higher in women who did not become clinicallypregnant. We conclude that vaginal progesterone alone providessufficient luteal support in GnRHa/HMG induced IVF cycles. Thecombination of vaginal progesterone and HCG as luteal supportleads to significant high luteal oestradiol and progesteroneconcentrations. But a high concentration of oestradiol seemsto have a deleterious effect on the implantation process, resultingin a low pregnancy rate.     

Analysis of the bleeding pattern in assisted reproduction cycles with luteal phase supplementation using vaginal micronized progesterone

This study was designed to determine the effects of a vaginal micronized progesterone preparation on bleeding patterns and pregnancy outcomes after in-vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI). The study population consisted of 149 consecutive women who had undergone IVF-ICSI using 'long-protocol' stimulation with buserelin-human menopausal gonadotrophin (HMG). A retrospective chart analysis of computerized medical records was undertaken. Vaginal progesterone (200 mg three times daily) was begun the day before oocyte retrieval and continued for a minimum of 16-19 days following human chorionic gonadotrophin (HCG) administration. Occurrence of bleeding following HCG injection, pregnancy rate and outcomes, and serum concentrations of oestradiol were measured. Women undergoing IVF and embryo transfer with ICSI and using vaginal progesterone for luteal support had normal luteal phase lengths (day of HCG minus day of onset of bleeding). In the absence of pregnancy, bleeding occurred after 19.2 +/- 3.9 days (mean +/- SD). Out of the pregnant group only three women bled within 19 days of HCG administration: two had biochemical pregnancies which spontaneously vanished and one evolved to term. The results reflect the normal bleeding pattern to be expected when vaginal progesterone is used for luteal support in IVF and embryo transfer, an approach whose efficacy has been amply proven. No shortened luteal phases were observed using vaginally administered progesterone.     

No evidence of increased uterine vascular impedance with patient ageing following IVF

A study was conducted to determine if uterine vascular impedance increases with advancing age in women undergoing ovarian stimulation for IVF. A group of 162 women who had undergone conventional IVF and embryo transfer was subdivided into three subgroups by age: 30-34 years (n = 49), 35-39 years (n = 79) and 40-44 years (n = 34). The pulsatility index (PI) and resistance index (RI) of the right and left uterine arteries were measured at baseline, on the day of oocyte retrieval, and at the mid-luteal phase. There were no differences in the average PI or RI by age at any phase of the cycle. In all age groups, the luteal phase values of PI and RI were lower than those observed earlier in the cycle. Endometrial thickness was not associated with age. There was no significant correlation between PI, RI and serum oestradiol and progesterone concentrations at any phase of the cycle. Ovarian response, as measured by average number of oocytes retrieved, decreased significantly with age. Thus, reduced pregnancy rates in older women undergoing ovarian stimulation are more likely to occur because of oocyte quality and quantity rather than uterine senescence. If future studies determine that the use of ovarian stimulation does decrease implantation rates more in older versus younger women, a mechanism other than increased uterine vascular impedance must be sought.     

黄体中期E2变化对IVF-ET结局的影响

目的研究黄体中期（ET后第3日）E2变化对IVF—ET结局的影响。方法放免法检测270例首次行IVF—ET助孕患者注射HCG日和黄体中期的外周血E2水平，根据黄体中期E2变化分为增高组（Group Ⅰ）和降低组（GroupⅡ），GroupⅡ又根据E2降低百分比进一步分为A、B、C、D四组，比较各组的种植率和临床妊娠率。结果GroupⅠ和GroupⅡ之间以及A、B、C、D各组间的种植率和临床妊娠率均无显著统计学差异（P〉0．05）。临床妊娠组和未妊娠组在HCG日和黄体中期E2水平、黄体中期E2升高比率和降低比率方面均无显著统计学差异（P〉0．05）。结论单纯评价黄体中期E2水平变化不能预测IVF—ET结局。     

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

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

The levels of C-reactive protein in women treated by IVF

BACKGROUND: The complex regulation of endometrial receptivity and embryo implantation involves cytokines, several of which are stimulators of the acute-phase reactant C-reactive protein (CRP). The purpose of this study was to evaluate the concentrations of serum CRP in women treated by IVF. METHODS: Seventy-two women who underwent IVF treatment were prospectively studied. The levels of serum CRP were evaluated on the following days: oocyte retrieval, embryo transfer, 5, 6 or 7 days afterwards and 12 days after embryo transfer. RESULTS: CRP levels increased from 6.8 +/- 9.5 mg/l on oocyte retrieval day to 14.6 +/- 12.5 mg/l on days 5-7 post-transfer (P<0.0001). The ratios of CRP levels for transfer day/pick-up day were 1.2 in women who conceived versus 2.5 in the non-pregnant group (P=0.01). CONCLUSION: In women treated by IVF the concentrations of CRP in blood increase significantly during the first week following oocyte retrieval. Successful outcome is associated with a relative small increment in CRP on the day of embryo transfer.     

Effect of follicular aspiration on hormonal parameters in patients undergoing ovarian stimulation

The effect of follicular aspiration and oocyte retrieval on hormonal parameters was examined in women undergoing ovarian stimulation for in-vitro fertilization (IVF) compared to induced ovulation in women undergoing ovarian stimulation for intrauterine insemination (IUI). Blood samples were collected immediately before and 1 h after oocyte retrieval and 48 h later on the day of embryo transfer in 25 IVF patients and before the insemination and 48 h later in 20 IUI patients. A highly significant fall in serum levels of oestradiol (E2), progesterone (P) and human chorionic gonadotrophin (HCG), (P less than 0.001) was observed in the IVF group 1 h after follicular aspiration. The decline in serum E2 levels was maintained at 48 h. In contrast, there was no significant change in serum E2 levels in the IUI group during 48 h. The immediate decline in E2 levels after follicular aspiration might play a role in preventing ovarian hyperstimulation syndrome.     

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.     

Progesterone supplementation increases luteal phase endometrial thickness and oestradiol levels in in-vitro fertilization.

Luteal phase supplementation with natural progesterone appears to increase the pregnancy rate in in-vitro fertilization (IVF). The objective of this investigation was to examine the effect of intravaginal progesterone on endometrial thickness and hormonal parameters 7-9 days after embryo transfer. IVF patients receiving progesterone supplementation (Prog +, n = 64), who did not conceive, were compared to patients not receiving progesterone (Prog -, n = 23) because of failed fertilization. These two groups were also compared to 20 women (Preg) who conceived and to 16 women (control) in the mid-luteal phase of natural cycles. Endometrial thickness was greater (P < 0.01) in the Prog + (0.88 +/- 0.04 cm) and Preg (0.92 +/- 0.02 cm) groups compared to the Prog - (0.71 +/- 0.05 cm) and control (0.65 +/- 0.05 cm) groups. Mean luteal phase serum oestradiol levels were also higher (P < 0.05) in the Prog + (1118 +/- 112 pmol/l) and Preg (2267 +/- 757 pmol/l) groups than in the Prog - (574 +/- 70 pmol/l) and control (468 +/- 38 pmol/l) groups. These findings suggest that progesterone supplementation may affect pregnancy rates in IVF by increasing endometrial thickness, thereby enhancing receptivity for implantation. The mechanism through which this effect occurs is unclear but may involve serum oestradiol elevation.     

Natural cycle IVF in unexplained, endometriosis-associated and tubal factor infertility.

BACKGROUND: To elucidate possible differences between unexplained and minimal peritoneal endometriosis-associated infertility, we studied their outcome in natural cycle IVF (NIVF). METHODS: A prospective cohort study was carried out on unexplained (33 couples), minimal peritoneal endometriosis-associated (30 couples) and tubal factor (24 couples) infertility in 223 NIVF cycles, using human chorionic gonadotrophin (HCG) for ovulation induction. RESULTS: During the first NIVF attempt, follicular and luteal phase oestradiol, FSH, LH and progesterone concentrations, as well as endometrial thickness and follicular diameter were similar among the three groups. Periovulatory follicular growth monitored from day of HCG administration to oocyte aspiration was significantly lowered in unexplained infertility compared with minimal endometriosis-associated and tubal factor infertility. The fertilization rate, clinical pregnancy rate per initiated cycle, per successful oocyte retrieval and per embryo transfer, in minimal endometriosis (80.0, 10.4, 16.0 and 23.5% respectively) were similar to that in tubal factor infertility patients (68.6, 5.8, 11.4 and 16.0%) but significantly higher (P < 0.05) than that of the unexplained infertility group (62.2, 2.6, 5.4 and 8.7%). CONCLUSIONS: The significant reduction in follicular periovulatory growth, fertilization and pregnancy rates in unexplained infertility compared with minimal peritoneal endometriosis patients may be explained by sub-optimal follicular development with possibly reduced oocyte quality, intrinsic embryo quality factors or by impaired implantation. From a clinical point of view, NIVF is less suited to unexplained infertility treatment, but might represent an interesting treatment option for minimal peritoneal endometriosis-associated infertility.     

A prospective randomized study on oestradiol valerate supplementation in addition to intravaginal micronized progesterone in buserelin and HMG induced superovulation

A prospective randomized study was conducted to evaluate theuse of adding oestradiol valerate 6 mg per os daily to intravaginalmicronized progesterone (600 mg daily) as luteal supplements.The study comprised 378 infertile women superovulated with agonadotrophin releasing-hormone agonist (GnRHa) and human menopausalgonadotrophins (HMG) for in-vitro fertilization (IVF) or zygoteintra-Fallopian transfer (ZIFT). The clinical pregnancy ratewas similar (29%) whether or not oestradiol valerate was addedto intravaginal progesterone. Eighteen out of twenty-two endometrialbiopsies were in phase, and morphological evaluations of thetwo luteal supplementation groups were not different. Serumhormone profiles in singleton pregnancies showed a similar dayof appearance of human chorionic gonadotrophin (HCG) in bothprotocols but significantly lower oestradiol concentrationsarose in the group without oestradiol valerate. In 32% of thesingleton pregnancies, the first appearance of HCG occurredlater than day 12 after HCG injection; in those ongoing pregnancies,corpus luteum rescue—as measured by significantly lowerserum oestradiol and progesterone concentrations—was compromised.This study provided no evidence of any benefit of routinelysupplementing GnRHa/HMG cycles with oestradiol valerate in additionto intravaginal micronized progesterone.     

Serum levels of free androstenedione, testosterone and oestradiol are lower in the follicular phase of conceptional than of non-conceptional cycles after ovarian stimulation with a gonadotrophin-releasing hormone agonist protocol.

Serum concentrations of total and free androstenedione, testosterone and oestradiol were followed during the follicular phase in women undergoing ovarian stimulation for treatment by in-vitro fertilization and embryo transfer (IVF-ET) and compared to those in natural unstimulated cycles. In addition, 10 conceptional and 18 non-conceptional cycles were compared in an attempt to understand the background for successful IVF cycles. The ultra-short gonadotrophin-releasing hormone agonist protocol was used for ovarian stimulation. Throughout the follicular phase, levels of total and free androstenedione and oestradiol were significantly lower in conceptional than in non-conceptional IVF cycles. In addition, levels of free testosterone during the follicular phase were significantly lower in women who conceived compared to non-conceptional IVF cycles, whereas levels of total testosterone were similar. Levels of both free and total androstenedione increased significantly from the second day of the menstrual cycle until oocyte retrieval in non-conceptional IVF cycles, whereas levels in conceptional IVF cycles and unstimulated cycles showed no increase. On the day of oocyte retrieval levels of free and total androstenedione were significantly higher in non-conceptional IVF cycles than in conceptional IVF cycles and unstimulated cycles, which were similar. This study suggests that appropriate levels of free biologically active androgens and oestradiol are important parameters for successful conception.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Long oestradiol replacement in an oocyte donation programme

The objective of this study was to optimize, in terms of endometrialreceptivity (embryo implantation), the limits of unopposed administrationof oestrogens beyond 35 days in an in-vitro fertilization (IVF)and ovum donation programme. Oocytes donated by 182 women undergoingIVF were distributed among 186 women treated by ovum donation.Five groups of recipients were established according to theduration of oestradiol valerate administration, in a ‘prolongedfollicular phase’ protocol, before embryo replacement,employing oestradiol valerate at increasing doses up to 6 mg/day.Gonadotrophin-releasing hormone analogues (GnRHa) were simultaneouslyadministered in ovulatory patients. The dosage of oestradiolvalerate was maintained until oocytes were available for inseminationand subsequent transfer. Donors and recipients were equallydistributed among groups in terms of age and cause of infertility.There was no difference among groups in serum oestradiol concentrationthe day in which progesterone was added to obtain a secretorytransformation of the endometrium. An analysis of the ovum donationcycles showed no difference among groups in pregnancy and implantationrates after the replacement of a similar number of embryos.Successful implantation was observed even after 100 days ofunopposed oestradiol valerate administration. Break-throughbleeding increasingly appeared according to the duration ofoestrogen replacement. These clinical observations provide evidencethat the concept of ‘prolonged follicular phase’oestrogen replacement for ovum donation can be maintained, atleast as long as 15 weeks. However, because of the high (>44%)incidence of break-through bleeding after 9 weeks, it is advisableto stop oestrogen treatment at this point. This protocol enormouslyfacilitates the chances of synchronization between donor andrecipient in an anonymous oocyte donation programme.     

Profound LH suppression after GnRH antagonist administration is associated with a significantly higher ongoing pregnancy rate in IVF

BACKGROUND: The significance of suppressed LH levels in GnRH antagonist cycles for IVF outcome is currently unknown. The purpose of this study was to evaluate prospectively the association between LH levels and ongoing pregnancy achievement after GnRH antagonist initiation in IVF cycles. METHODS: Ovarian stimulation with a fixed dose of 200 IU recombinant FSH and daily GnRH antagonist (ganirelix) 0.25 mg from day 6 of stimulation was initiated in 116 women. Patients were not pretreated with an oral contraceptive. Induction of final oocyte maturation was performed with HCG 10,000 IU as soon as three follicles of > or =17 mm were present in ultrasound, and was followed by oocyte pick-up, conventional IVF or ICSI, and embryo transfer. The luteal phase was supplemented with vaginal progesterone. RESULTS: A significant decrease of both ongoing pregnancy rate and implantation rate was present across groups of patients with increasing LH levels. The highest implantation rate and ongoing pregnancy rate was present in those patients with LH levels on day 8 of stimulation < or =0.5 IU/l. CONCLUSIONS: Profound suppression of LH on day 8 of stimulation is associated with a significantly higher chance of achieving an ongoing pregnancy. More studies are necessary to evaluate this phenomenon further.     

Implantation: Clinical evidence for a detrimental effect on uterine receptivity of high serum oestradiol concentrations in high and normal responder patients

This study was undertaken to investigate an empirical observationthat ‘high responder patients have poorer in-vitro fertilization(IVF) outcome than normal responder patients’. The aimof our study was to analyse the effect of high serum oestradioland progesterone concentrations at the day of human chorionicgonadotrophin (HCG) administration on endometrial receptivityand oocyte—embryo quality in high and normal responderpatients. The IVF patients were divided into two groups: 59high responder patients who voluntarily donated some of theiroocytes, and a control group consisting of 105 normal responderpatients. Both groups were compared in terms of the number andquality of oocytes retrieved, embryos transferred, fertilization,implantation and gestation rates, serum oestradiol and progesteroneconcentrations and the oestradiol: progesterone ratio on theday of HCG injection. To ascertain oocyte—embryo quality,a second control group of 96 women undergoing oocyte donation(receiving oocytes from high responder patients) was considered.To assess the impact of steroid concentrations on endometrialreceptivity, high responder patients were divided into two subgroupsaccording to oestradiol concentration, above or below the minimaloestradiol and progesterone concentrations (mean – SD)in this group. The normal responder patients were divided intotwo subgroups according to oestradiol concentration, above orbelow the maximal oestradiol and progesterone concentrations(mean + SD) in this group. To assess further the relevance ofoestradiol concentration on endometrial receptivity, patientswere divided into different subgroups according to increasingoestradiol concentration, regardless of whether they were highor normal responders. High responder patients had significantlydecreased implantation and pregnancy rates per cycle comparedwith normal responder patients (33.3 versus 16.3 and 11.1 versus5.4% respectively; P < 0.05). The results of 108 embryo transfersin 91 recipients who received oocytes from the high respondergroup showed normal embryo quality. Implantation rates and pregnanciesper cycle were significantly lower in high responder patientswith serum oestradiol concentrations > 1700 pg/ml comparedwith those having oestradiol concentrations 1700 pg/ml, as wellas in normal responder patients with serum oestradiol concentrations2200 pg/ml compared with those having oestradiol concentrations<2200 pg/ml. Considering all the patients together, significantdecreases in pregnancy and implantation rates were observedwhen oestradiol concentrations were >2500 pg/ml comparedwith patients having lower oestradiol concentrations. Our clinicalresults demonstrate that high serum oestradiol concentrationson the day of HCG injection in high and normal responder patients,regardless of the number of oocytes retrieved and the serumprogesterone concentration, are detrimental to uterine receptivitywithout affecting embryo quality.     

Sex hormone-binding globulin, oestradiol-17 beta, progesterone and testosterone at stimulation and after embryo transfer during in-vitro fertilization.

Serum concentrations of sex hormone-binding globulin (SHBG), oestradiol-17 beta progesterone and testosterone were measured in 23 gonadotrophin-stimulated menstrual cycles and in the implantation period [days 11-19 after human chorionic gonadotrophin (HCG) injection] following in-vitro fertilization and embryo transfer. Nine cycles resulted in successful pregnancies, one pregnancy ended in spontaneous abortion (week 14) and 13 cycles were without conception. SHBG levels were significantly elevated above pretreatment values from day 3 after HCG injection onwards. A significant positive correlation was found between increments in SHBG (delta SHBG) during the luteal phase and oestradiol/testosterone ratios during the follicular and luteal phases. In the pregnant cycles a significant positive correlation was also found between delta SHBG during the implantation period and oestradiol/testosterone ratios during the luteal phase and the implantation period. Significant negative correlations were found between delta SHBG and testosterone during the luteal phase in pregnant and non-pregnant women as well as between delta SHBG during the period corresponding to implantation and testosterone during the luteal phase in non-pregnant cycles. The results may reflect a modulating action of the oestrogen/androgen balance upon SHBG levels in subjects with supraphysiological oestradiol levels, such as in stimulated cycles and in very early pregnancy.     

Colour Doppler indices of follicular blood flow as predictors of pregnancy after in-vitro fertilization and embryo transfer.

Peak systolic velocity (PSV) of individual follicles has been correlated with oocyte recovery, fertilization rate and embryo quality [in women undergoing in-vitro fertilization (IVF) and embryo transfer]. The present study assessed the role of quantitative and qualitative indices of follicular vascularity in predicting pregnancy after IVF and embryo transfer. A total of 106 women undergoing IVF treatment for infertility who were considered to be at risk of failure (>37 years of age, history of low response to gonadotrophin stimulation, or multiple failed IVF cycles) constituted the study group. PSV was measured from the three largest follicles on both the right and left ovaries on the day of human chorionic gonadotrophin (HCG) administration using an Acuson Sequoia with a 4-8 MHz transvaginal probe. The quality of follicular flow was graded from 1 to 4 according to the amount of visible colour flow around the follicle (grade 1 when one-quarter of the follicle, grade 2 when one-half, grade 3 when three-quarters, and grade 4 when the entire follicle was surrounded by colour). Clinical pregnancies resulted in 11 (10%) of the 106 high-risk women. Women who had PSV >/= 10 cm/s in at least one follicle on the day of HCG administration more often became pregnant than those with PSV <10 cm/s (P = 0.05). All pregnancies occurred in women with grade 3 or 4 follicular blood flow. Qualitative as well as quantitative measurements of follicular flow predict pregnancy after IVF and embryo transfer.     

The luteal phase after in-vitro fertilization and related procedures

To evaluate any beneficial effect of progesterone supplemen–tationduring the luteal phase of GIFT or IVF cycles stimulated byclomiphene citrate and HMG, two random prospective studies wereperformed. In the first study, a group of patients receiveda luteal phase supplement of 50 mg natural progesterone i.m.daily from the day of oocyte retrieval onwards. Initial resultson 168 patients indicated that the pregnancy rate was similarin patients with or without progesterone supplements. No differenceswere found between the two groups in an analysis of pregnantand failed cycles. In a second study two different protocolsof luteal phase sup–plementation after Buserelin–HMGstimulation were com–pared: natural progesterone in combinationwith oestradiol valerate (50 patients) or HCG supplements (41patients). A 32% pregnancy rate per cycle was encountered inboth groups. Endometrial biopsies, taken during the luteal phasefrom patients who did not undergo embryo replacement, revealedretarded endometrial development in most of the biopsies.