Ovary and Ovulation: Contralateral selection of dominant follicle favours pre-embryo development

Ovulation was studied using vaginosonography in a total of 410natural cycles of 123 women undergoing infertility treatment[267 intrauterine insemination (IUI) cycles of 103 women and143 in-vitro fertilization (IVF) cycles of 50 women]. None ofthe women received ovarian stimulation. Each follicle was measureddaily from 14 mm in diameter until formation of corpus luteumor oocyte retrieval. Contralateral ovulation as compared withthe preceding cycle occurred in 57% of the 410 cycles. Contralateralovulations occurred in 72% of cycles with a follicular phase<13 days. In cycles with a follicular phase of >14 days,ovulations occurred at random. The length of follicular phasein contralateral ovulation cycles (15.2 ± 3.2 days) wassignificantly (P < 0.05) shorter than that of ipsilateralovulation cycles (15.8 ± 2.8). During the 57% contralateralovulations in 143 IVF cycles, the rates of oocyte retrieval(89%), fertilization (69%), cleavage (90%) and embryo transfer(56%) were significantly higher than those of ipsilateral ovulations(69, 51, 64 and 23% respectively). The pregnancy rate of contralateralovulations (9%) was also higher, though not significantly, thanthat of ipsilateral ovulations (3%), although the pregnancyrates per transfer were similar (16 and 14% respectively). Thetotal pregnancy rate of both IUI and IVF was higher in contralateralthan in ipsilateral ovulation cycles (8.1 and 4.0% respectively).The dominant follicles in contralateral ovulation cycles showedsignificantly higher oestradiol/androstenedlone ratio (P <0.025) and oestradlol/testosterone + androstenedione ratio (P< 0.025), and lower androstenedione (P < 0.05) than thoseof ipsilateral ovulation cycles. There was no significant differencein oestradiol, progesterone and testosterone. These resultsindicate that the dominant follicles in contralateral ovulationcycles are healthier than those of ipsilateral ones. Local intra-ovarianfactors, e.g. from the corpus luteum, may negatively affectthe health of the dominant follicle and the enclosed oocyte.Therefore contralateral selection of the dominant follicle inthe succeeding cycle may favour pre-embryo development. Thechance of conceiving during a natural cycle may be affectedby the site of ovulation in the preceding cycle.     

Assessment of changes in volume and vascularity of the ovaries during the normal menstrual cycle using three-dimensional power Doppler ultrasound

BACKGROUND: Our aim was to describe changes in the volume and vascularization of both ovaries, the dominant follicle and the corpus luteum during the normal menstrual cycle using three-dimensional (3D) power Doppler ultrasound. METHODS: Fourteen healthy volunteers underwent serial transvaginal 3D ultrasound examinations of both ovaries on cycle day 2, 3 or 4, then daily from cycle day 9 until follicular rupture and 1, 2, 5, 7 and 12 days after follicular rupture. The volume and vascular indices of the ovaries, the dominant follicle and the corpus luteum were calculated off-line using virtual organ computer-aided analysis (VOCAL) software. RESULTS: The volume of the dominant ovary increased during the follicular phase, decreased after follicular rupture and then increased again during the luteal phase. Vascular indices in the dominant ovary and the dominant follicle/corpus luteum increased during the follicular phase, the vascular flow index (VFI) in the dominant follicle being on average (median) 1.7 times higher on the day before ovulation than 4 days before ovulation (P=0.003). The vascular indices continued to rise after follicular rupture so that VFI in the corpus luteum was on average (median) 3.1 times higher 7 days after ovulation than in the follicle on the day before ovulation (P=0.0002). The volume and vascular indices in the non-dominant ovary manifested no unequivocal changes during the menstrual cycle. CONCLUSIONS: Substantial changes occur in volume and vascularization of the dominant ovary during the normal menstrual cycle. 3D power Doppler ultrasound may become a useful tool for assessing pathological changes in the ovaries, for example, in subfertile patients.     

The effect of accompanying dominant follicle development/ovulation on the outcomes of frozen-thawed blastocyst transfer in HRT cycle

The artificial regime was widespread used in frozen-thawed embryo transfer (FET). Some researchers asserted that if dominant follicles developed or ovulation occurred in hormone replacement FET cycles, this cycle should be cancelled because the fitting timing of transfer was hard to determine. In this study, we compared the difference between the outcome of frozen-thawed blastula transfer in hormone replacement treatment cycle (HRT) with or without dominant follicle development/ovulation. A total of 171 cases of frozen-thawed blastula transferred successfully in HRT cycle were retrospectively analyzed. Patients were divided into three groups according to dominant follicle development, ovulation or not: Group A, cycles without dominant follicle developing. Group B, cycles with dominant follicle developing but without ovulation. Group C, ovulated cycles. The results showed that there was no significant difference in the pregnancy rates or other parameters among the three groups, but the abortion rate was higher in group C than those of other two groups. To conclude, dominant follicle development/ovulation was not the necessary indication to cancel transfer cycles in HRT cycles, and our cautious decision would save many valuable cycles.     

High ovulatory rates with use of troglitazone in clomiphene-resistant women with polycystic ovary syndrome.

This preliminary report reviews our experience with 18 infertile patients with clomiphene-resistant polycystic ovary syndrome (PCOS). In the first treatment cycle, troglitazone was administered alone. During cycles 2-5, clomiphene was added with increments of 50 mg (up to 200 mg/day) if the previous cycle was anovulatory. Basal body temperature charts and serum progesterone were obtained to confirm ovulation. In a total of 66 treatment cycles, ovulation occurred in 44 (67%) and pregnancy in seven (11%). There were no significant changes in body weight, waist:hip ratio or liver enzymes during treatment. Troglitazone, alone or with clomiphene, induced ovulation in 15 of 18 patients (83%) and seven (39%) of them achieved pregnancy. This is the first report on ovulatory rates in clomiphene-resistant women with PCOS when troglitazone was used alone or with clomiphene. Recently, metformin and clomiphene were successfully used in women with PCOS. However, our patients represent a more resistant population of women with PCOS, with each patient serving as her own historical control by previous resistance to clomiphene. Although the pregnancy rate (39%) was promising for clomiphene-resistant women with polycystic ovary syndrome, it does not seem to have a definite advantage over gonadotrophins.     

Contralateral ovulation shortens follicular phase length and favours pre-embryo development during ovarian stimulation with clomiphene citrate

The present study was undertaken to evaluate whether the site of ovulation affects the following follicular phase length and pre-embryo development during infertility treatment with ovarian stimulation using clomiphene citrate. A total of 363 cycles in 97 patients undergoing infertility treatment (182 intrauterine insemination (IUI) cycles in 60 patients and 181 in-vitro fertilization (IVF) cycles in 52 patients) were studied. The cycles were divided into two main groups: preceding unilateral ovulation (PUO) and preceding bilateral ovulation (PBO). In the PUO group, the cycles were subdivided into contralateral ovulation, bilateral ovulation and ipsilateral ovulation. In IVF cycles alone, bilateral ovulations were further divided into bilateral ovulation- contralateral side and bilateral ovulation, ipsilateral side. Contralateral ovulations were seen in 134 of 240 cycles (56%), excluding bilateral ovulation and PBO. The follicular phase length in contralateral ovulation (16.2 +/- 2.6 days, mean +/- SD) was significantly (P < 0.05) shorter than that of ipsilateral ovulation (16.9 +/- 2.8). There were no significant differences of follicular phase length among contralateral ovulation, bilateral ovulation and PBO. Of IVF cycles including contralateral ovulation-ipsilateral ovulation and bilateral ovulation a total of 107 preovulatory follicles was assessed in the contralateral side (contralateral ovulation + bilateral ovulation-contralateral side) and 97 in the ipsilateral side (ipsilateral ovulation + bilateral ovulation, ipsilateral side). The oocyte retrieval rate (88%), fertilization rate (84%), cleavage rate (95%), embryo transfer rate (70%) of contralateral follicles were higher than those of ipsilateral follicles (71, 62, 86, 38% respectively) and those of PBO (76, 62, 87, 41% respectively). The total pregnancy rate of both IUI and IVF did not differ among contralateral ovulation (15%), ipsilateral ovulation (8%), bilateral ovulation (11%) and PBO (10%). The results confirm and extend our previous findings in natural cycles, suggesting that local ovarian factors, e.g. from corpus luteum, affect the health of preovulatory follicle and the enclosed oocyte in the same ovary (ipsilateral) negatively. Contralateral selection of preovulatory follicles in the succeeding cycle shortens the follicular phase length and favours pre- embryo development. The chance of conceiving during ovarian stimulation with clomiphene citrate may thus be affected by the site of ovulation in the previous cycle.      

Relationship of constructed follicular growth patterns in stimulated cycles to outcome after IVF

The growth patterns of 827 follicles have been constructed from ultrasound measurements made between day -7 and day -2 of the follicular phase (oocyte aspiration = day 0) as a part of the routine treatment of 107 in-vitro fertilization (IVF) patients. A distinctive pattern of growth which was characterized by rapid early growth and a later growth consistent with the 'conceptual pattern' of growth described by Zegers-Hochschild (1984) for natural cycles was shown to be highly correlated with a delivered pregnancy outcome. Every cycle where a delivered pregnancy resulted (n = 9) produced one or more follicles with this pattern of growth (11/69 follicles, 16%). In contrast, only 20% (20/98) of cycles with any other outcome (abnormal pregnancy, no pregnancy, no embryo formed) appeared to have a follicle conforming to this pattern (27/758 follicles, 3.6%). These observations suggest that the follicle growth pattern, with particular emphasis on the rate of early growth, may be a highly predictive indicator of the quality of follicle development and the subsequent pregnancy potential of the oocyte contained within.     

Pure FSH for ovulation induction in patients with polycystic ovary syndrome and resistant to clomiphene citrate therapy

Twenty-nine infertile women with polycystic ovary disease whichwas resistant to therapy with clomiphene citrate underwent acombined treatment for follicle recruitment consisting of pureFSH during the first days of the cycle and HMG during the lastdays of the follicular phase. Sixty cycles were stimulated ofwhich 83% were ovulatory. Eighteen pregnancies were achieved(36% of cycles, 62% of patients). The multiple pregnancy ratewas 39%. Twelve cycles (20%) showed the ovarian hyperstimulationsyndrome (OHS) although seven of these resulted in full termdeliveries. There were no miscarriages among the patients studied.     

Ovary and ovulation: Folliculocentesis: a novel research technique to investigate the intrafollicular endocrine microenvironment

During development of the dominant follicle, the avascular granulosacells and oocyte are exposed to the follicular fluid endocrinemicroenvironment. An alteration in the endocrine characteristicsof follicular fluid affects follicular steroidogenesis, oocytematuration, ovulation and subsequent corpus luteum function.In-vitro studies on pooled follicular fluid from ovarian specimenslacked temporal precision between menstrual and follicular endocrineevents. We have established a new technique, termed folliculocentesis(FC), to sample follicular fluid from the dominant ovarian folliclewithout compromising its growth or function during the mid-to late follicular phase. A total of 38 subjects with regularovulatory cycles each underwent two identical cycles of hormoneand follicle growth monitoring: one cycle served as the control,and FC was performed during the second cycle. During all cycles,plasma luteinizing hormone (LH), oestradiol and ultrasound monitoringof follicle growth were commenced on day 7 and continued untilafter ovulation. During FC cycles, 200 ul of follicular fluidwere aspirated from the dominant follicle using transvaginalultrasound guidance when the follicle diameter reached 10 mm.Six subjects were excluded from the study because of incompleteor invalid endocrine data. In all, 32 subjects completed boththe FC and control cycles. The follicle growth pattern, maximumfollicle diameter, plasma oestradiol, oestradiol peak, plasmaLH, LH surge and follicular phase length were similar duringFC and control cycles. A total of 50 valid follicular fluidsamples were obtained when the dominant follicle was sampledonce, twice or three times during the same cycle and from thesame follicle in 15, 16 and one subjects respectively. The follicularfluid samples contained steroid concentrations consistent withthose of the mid- to late follicular phase. We conclude thatthe FC procedure is safe, easy to perform and does not affectfollicle growth or hormone dynamics. Analysis of the follicularfluid samples is expected to provide us with valuable in-vivoinformation about ovarian endocrinology.     

Characteristics of human ovulation in natural cycles correlated with age and achievement of pregnancy.

BACKGROUND: The aim of this study was to evaluate whether characteristics of human ovulation correlate with age and pregnancy potential. METHODS: Two groups of women with regular menstrual cycles were included (i.e. one fertile and one infertile group), which were divided into four age groups (< or =29, 30-34, 35-39, > or = 40 years). Monitoring included observations of follicular phase length, whether ovulations occurred from the left or right ovary, the pattern of ovulations in succeeding natural cycles and, in a subset of women, early follicular phase FSH concentrations. RESULTS: Ovulation moving from one ovary to the other in two consecutive cycles (i.e. contralateral ovulation) was inversely correlated with age, showing a ratio of contralateral ovulation per contra plus ipsilateral ovulations (C/C+I) of 62% in women <29 years, gradually decreasing to 42% in women >40 years. The ratio of right-sided ovulation per right plus left-sided ovulations (R/R+L) was unrelated to age and remained almost constant at a level of approximately 55%. The follicular phase length was inversely correlated with age, being 16.2 +/- 2.9, 15.4 +/- 2.9, 14.8 +/- 2.8 and 13.7 +/- 1.3 days in women < 29, 30-34, 35-39 and >40 years of age respectively. The follicular phase length was similar when comparing ovulations occurring from the right and left ovary, but comparing two successive cycles, the length of the follicular phase of the second cycle, showing contralateral ovulation, was shorter than ipsilateral ovulation with two consecutive ovulations in the same ovary. The pregnancy rate of the four groups decreased with age, being 14, 12, 5 and 3% respectively. The C/C+I ratio correlates with pregnancy rate and follicular phase length, and inversely correlates with basal FSH, whereas R/R+L is unrelated to age and pregnancy rate. CONCLUSIONS: Human ovulation shows characteristics related to age. The interaction between the two ovaries seems to be most pronounced in the younger years, where ovulations jump from one ovary to the other more frequently than later on in life. The C/C+I ratio shows a clear correlation with age and pregnancy rate.     

Do cycle disturbances explain the age-related decline of female fertility? Cycle characteristics of women aged over 40 years compared with a reference population of young women

BACKGROUND: The cause of declining fertility with age, in women who still have regular menstrual cycles, is not clear. METHODS: Follicle development, endometrial growth and hormonal patterns were evaluated in cycles of older women (aged 41-46 years; n = 26) who previously were normally fertile, and these cycles were compared with a reference group of relatively young fertile women (aged 22-34 years; n = 35). RESULTS: Clearly abnormal cycles were found in only two women in the older age group, and in one woman in the younger group. The main differences between the age groups were a shorter follicular phase and cycle length in the older group, in combination with higher FSH levels in the late luteal and early follicular phase. In contrast to published data which suggest an "accelerated" follicle development in older women, sonographical and hormonal evidence was found of an "advanced" follicle growth, with an earlier start already during the luteal phase of the preceding cycle, and an advanced selection and ovulation of the dominant follicle. CONCLUSIONS: Such an earlier start of follicle growth in a possibly less favourable hormonal environment, as well as a limited oocyte pool, may contribute to a decreased follicle and oocyte quality, resulting in diminished fertility in ageing women.     

Low-dose gonadotrophin therapy for induction of ovulation in 100 women with polycystic ovary syndrome.

Women with anovulation due to polycystic ovary syndrome are likely to develop multiple follicles during gonadotrophin therapy and therefore have a high risk of multiple pregnancy. We have developed a low-dose regimen for use in these women; 100 women with clomiphene-resistant polycystic ovary syndrome were treated. Ninety-five of the women ovulated at least once, 72% of the 401 cycles induced were ovulatory and the majority (73%) of these were uni-ovulatory. The overall cumulative conception rate was 55% at 6 months with only two multiple pregnancies. The rate of early pregnancy loss was 32%, which is similar to that reported by other groups. The prevalence of complications was low with no cases of severe hyperstimulation and less than 5% of cycles were abandoned because of development of multiple follicles. Analysis of baseline and mid-follicular luteinizing hormone levels showed that a raised baseline and/or mid-follicular luteinizing hormone level was associated with a poor response to treatment, i.e. anovulation, ovulation but no conception, or early pregnancy loss. There were no successful pregnancies in the women whose luteinizing hormone levels were persistently raised during ovulatory cycles. Low-dose gonadotrophin therapy is a safe and effective method of inducing ovulation; it is associated with a high incidence of single follicular development and a very low multiple pregnancy rate.     

Controlled ovulation of the dominant follicle: a critical role for LH in the late follicular phase of the menstrual cycle

BACKGROUND: A method was sought to control ovulation of the dominant follicle and to test the importance of LH during the late follicular phase of the menstrual cycle. Menstrual cycles of rhesus monkeys were monitored, and treatment initiated at the late follicular phase (after dominant follicle selection, before ovulation). METHODS: The 2-day treatment consisted of GnRH antagonist plus either r-hFSH and r-hLH (1:1 or 2:1 dose ratio) or r-hFSH alone. In addition, half of the females received an ovulatory bolus of hCG. RESULTS: When treatment was initiated at estradiol levels >120 pg/ml, neither the endogenous LH surge, ovulation nor luteal function were controlled. However, when treatment was initiated at estradiol levels 80-120 pg/ml using either 1:1 or 2:1 dose ratios of FSH:LH, the LH surge was prevented, and ovulation occurred following hCG treatment. FSH-only treatment also prevented the LH surge, but follicle development appeared abnormal, and hCG failed to stimulate ovulation. CONCLUSIONS: Control over the naturally dominant follicle is possible during the late follicular phase using an abbreviated GnRH antagonist, FSH+LH protocol. This method offers a model to investigate periovulatory events and their regulation by gonadotrophins/local factors during the natural menstrual cycle in primates.     

Randomized comparison of ovulation induction with and without intrauterine insemination in the treatment of unexplained infertility

The aim of this prospective randomized controlled study wasto determine the possible role of ovulation induction with intrauterineinsemination (IUI) in the treatment of unexplained infertility.A total of 100 patients were randomized to receive ovulationinduction with or without IUI. All patients were treated withlong-course gonadotrophinreleasing hormone analogue (GnRHa),starting in the luteal phase, and exogenous follicle stimulatinghormone (FSH) to induce follicular growth. Ovulation was inducedusing human chorionic gonadotrophin and timed intercourse (TI)was advised 24–48 h later or IUI was effected 36—48h later. Both the cycle fecundities (21.8 and 8.5%) and thecumulative ongoing pregnancy rates after three cycles (42 and20%) were significantly higher (P < 0.03) in the IUI groupthan in the TI group respectively. This is a clear indicationthat ovulation induction with IUI is an effective treatmentmethod for unexplained infertility, but ovulation inductionwith TI has a negligible impact in this large group of patients.     

早卵泡期与优势卵泡后加用FSH方案治疗小卵泡排卵不孕疗效比较

目的比较早卵泡期与优势卵泡后加用FSH方案治疗小卵泡排卵的疗效。方法将小卵泡排卵62例102个治疗周期,随机分成2组：A组早卵泡期肌肉注射尿促卵泡激素（丽申宝FSH）。B组卵泡≥12mm时肌肉注射尿促卵泡激素（丽申宝FSH）。观察、比较2组的妊娠率、早期流产率等。结果 B组与A组相比妊娠率、早期流产率无明显差异,但多胎率及OHSS（卵巢过度刺激综合征）发生率明显低于A组。结论优势卵泡后加用FSH方案是有效且安全的治疗小卵泡排卵的促排卵方案。     

Side of ovulation and cycle characteristics in normally fertile women

This study was undertaken to establish whether ovulation in humans alternates consistently from right to left ovary in successive cycles and whether the site of ovulation affects the next cycle length or the hormonal profiles. A total of 199 cycles in 80 normally fertile women were studied. The volunteers were monitored with ultrasonography to determine the day and side of ovulation and to calculate follicular and luteal phase lengths. Urinary hormone concentrations were also assayed. Right-sided ovulations occurred in 104 of the 199 cycles (52.3%; not significantly different from 50%). Alternate ovulations occurred in 61 of the 119 pairs of succeeding cycles (51.3%, not significant). The follicular phase length in contralateral ovulation (14.59 +/- 0.33 days; mean +/- SEM) did not differ significantly from that of ipsilateral ovulation (14.59 +/- 0. 37 days). There were also no significant differences in urinary concentrations of oestrone-3-glucuronide, pregnanediol-3alpha glucuronide, follicle stimulating hormone, and luteinizing hormone between ipsilateral and contralateral ovulation in either early follicular, peri-ovulatory or luteal phase of the cycle. It is concluded that in normally fertile women, the cycle length and the hormonal profile are independent of the, most probably random, site of ovulation.     

Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study

BACKGROUND: The aim of this work was to evaluate the efficacy of adding dexamethazone (DEX) (high dose, short course) to clomiphene citrate (CC) in CC-resistant polycystic ovary syndrome (PCOS) with normal dehydroepiandrosterone sulphate (DHEAS) in induction of ovulation. METHODS: Eighty infertile women with CC-resistant PCOS were randomly assigned into two groups. Group I: Clomiphene citrate 100 mg/day was given from day 3 to day 7 of the cycle and DEX 2 mg/day from day 3 to day 12 of the cycle. Group II: Same protocol of CC combined with placebo (folic acid tablets) was given from day 3 to day 12 of the cycle. The main outcome was ovulation. Secondary measures included number of follicles >18 mm endometrial thickness and pregnancy rate. Ovarian follicular response was monitored by transvaginal ultrasound. HCG 10,000 U was given when at least one follicle measured 18 mm, and timed intercourse was advised. RESULTS: There were no statistically significant differences between groups as regards age, duration of infertility, BMI, waist-hip ratio (WHR), menstrual pattern, hirsutism, serum DHEAS or day of HCG administration. The mean number of follicles>18 mm at the time of HCG administration and the mean endometrial thickness were significantly higher in the DEX group than in the placebo group (P<0.05). Similarly, there were significantly higher rates of ovulation (75 versus 15%) (P<0.001) and pregnancy (40 versus 5%) (P<0.05) in the DEX group. Dexamethazone was very well tolerated as no patients complained of any side effect. There was a significant difference between the responders and non-responders in the presence of oligomenorrhea, amenorrhea or hirsutism. CONCLUSION: Induction of ovulation by adding DEX (high dose, short course) to CC in CC-resistant PCOS with normal DHEAS is associated with no adverse anti-estrogenic effect on the endometrium and higher ovulation and pregnancy rates in a significant number of patients. Induction with DEX appears to be independent on age, period of infertility, BMI or WHR.     

Women with polycystic ovary syndrome gain regular menstrual cycles when ageing

The aim of this study was to investigate if previously oligo- or amenorrhoeic polycystic ovary syndrome (PCOS) patients gain regular menstrual cycles when ageing. Women registered as having PCOS, based on the combination of oligo- or amenorrhoea and an increased LH concentration, were invited by letter to participate in a questionnaire by telephone. In this questionnaire we asked for the prevalent menstrual cycle pattern, which we scored in regular cycles (persistently shorter than 6 weeks) or irregular cycles (longer than 6 weeks). We interviewed 346 patients of 30 years and older, and excluded 141 from analysis mainly because of the use of oral contraceptives. The remaining 205 patients showed a highly significant linear trend (P < 0.001) for a shorter menstrual cycle length with increasing age. Logistic regression analysis for body mass index, weight loss, hirsutism, previous treatment with clomiphene citrate or gonadotrophins, previous pregnancy, ethnic origin and smoking showed no influence on the effect of age on the regularity of the menstrual cycle. We conclude that the development of a new balance in the polycystic ovary, solely caused by follicle loss through the process of ovarian ageing, can explain the occurrence of regular cycles in older patients with PCOS.     

The impact of ovarian cystectomy on ovarian response to stimulation during in-vitro fertilization cycles

This study was carried out to investigate whether ovarian cystectomyinterferes with follicular recruitment and the number of oocytesretrieved in an in-vitro fertilization (IVF) cycle. Patientswho had previously undergone unilateral ovarian cystectomy (n= 90) and control patients (n = 90) with no history of ovariansurgery were included in our study. The parameters comparedwere the number of follicles recruited and the number of oocytesobtained from each ovary. In patients who had undergone surgery,the normal ovaries recruited a significantly higher number offollicles (P < 0.001) and yielded a significantly highernumber of oocytes (P < 0.001) compared with the contralat-eralovaries which had undergone cystectomy. In the control patients,no significant differences were identified between the leftand right ovaries. These results demonstrate that ovarian cystectomyreduces follicle and oocyte numbers in ovulation induction cycles.     

Early resort to ovarian stimulation improves the cost-effectiveness of a donor insemination programme.

Women undergoing donor insemination (DI) are usually regularly ovulating, therefore the role of ovulation induction in this modality of treatment has been controversial. Some recent studies reported higher pregnancy rates in stimulated cycles in comparison with natural cycles. We employed a sequential step-up protocol in which treatment was started in a natural cycle, continued with a clomiphene citrate-stimulated cycle, and finished with an ovulation induction cycle. The patients were allowed three attempts at each step before moving to the next if conception did not occur. The aim of this protocol was to enhance the cost-effectiveness of the DI programme by increasing the cycle fecundability. A total of 101 patients underwent 216 cycles of DI, including 44 patients in 80 natural cycles, 38 patients in 89 CC-stimulated cycles, and 19 patients in 47 ovulation induction cycles. The clinical pregnancy rate per started cycle (CPR/C) and per patient during this period was 14% and 30% respectively. The pregnancy rates per started cycle and per patient in the natural, CC-stimulated and ovulation induction cycles were: 13 and 32%, 10 and 18%, and 21 and 53% respectively. There was no significant difference in the CPR/C in the three groups; however, the CPR per patient in the induced ovulation cycles was significantly higher than in the CC-stimulated cycles (P = 0.005). Only one patient during this period had a multiple pregnancy in the ovulation induction group, giving an overall multiple pregnancy of 3%. By using this treatment strategy, we achieved a high clinical pregnancy rate, a low multiple pregnancy rate and a low cost of treatment per pregnancy.     

Embryo quality in natural versus stimulated IVF cycles

BACKGROUND: The impact of controlled ovarian stimulation (COS) on oocyte and subsequent embryo quality remains controversial. In the present study we have compared embryo quality in natural and stimulated cycles in the same group of patients. METHODS: This retrospective study was comprised of patients with a regular menstrual cycle who had IVF after COS using rFSH in a long GnRH agonist protocol. In all stimulated cycles the patients had fresh embryos transferred and surplus good quality embryos cryopreserved. Subsequently the same patients were treated with a modified FER cycle (mFER) where thawing of the frozen embryos was combined with aspiration of the dominant follicle in the natural cycle. The embryo cleavage stage and quality score were compared between the stimulated and the natural cycle for the patients having an embryo in the natural cycle. RESULTS: In 177 cases patients returned for mFER in a natural cycle. Spontaneous ovulation had occurred in 35 cycles. In 17 cycles no oocyte was retrieved at aspiration and in 125 cycles 128 oocytes were aspirated. In the stimulated cycles from these patients we had obtained 950 embryos (cleavage rate 70.4%) versus 85 embryos (cleavage rate 66.4%) (P = 0.34) in the natural cycles. Comparing the embryos in the natural and stimulated cycles in all patients having an embryo in the natural cycle, we found no difference in the distribution between the different cleavage stages. Of the cleaved embryos, 53% in the stimulated cycles had >or=4 cells versus 59% in the natural cycles after 2 days culture (P = 0.31). In the stimulated cycles 61% of the embryos had <10% fragmentation at the time of transfer on day 2, compared to 69% in the natural cycles (P = 0.15). CONCLUSION: The administration of exogenous gonadotrophins was not reflected in cleavage capacity or quality assessment of the resulting embryos.