Human Reproduction, Vol. 14, No. 1, 96-100,
January 1999
© 1999 European Society of Human Reproduction and Embryology
Anovulations in an ovary during two menstrual cycles enhance the pregnancy potential of oocytes matured in that ovary during the following third cycle
1 Fukuda Ladies Clinic, 30–9 Kariya, Ako, Hyogo 678–0239, Japan and 2 Laboratory of Reproductive Biology, University Hospital of Copenhagen, Copenhagen, Denmark
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and methodsResultsDiscussionReferences |
|---|
The aim of this study was to test whether ovulation from an ovary affects the health of oocytes from dominant follicles in that ovary two cycles later. A total of 80 women each with two intact ovaries underwent 270 treatment cycles (155 natural cycles and 115 clomiphene citrate cycles) all showing unilateral ovulation. The results from the in-vitro fertilization (IVF) treatment were grouped according to whether ovulation (O) or anovulation (A) (no ovulation) was observed in the ovary with dominant follicle during the treatment cycle in the previous two cycles: O-O, A-O, O-A and A-A (previous second cycle-previous first cycle). The rate of pre-embryo formation in A-A was significantly higher than that of O-A. The pregnancy rate in A-A (29%) was also higher than those of O-A (13%), A-O (9%) and O-O (5%). These rates increased from O-O to A-A as the number of previous ovulations in an ovary decreased. The presence of a corpus luteum and/or a dominant follicle is likely to exert local negative effects on the health of the oocyte contained in the follicle selected to ovulate up to two cycles later. Anovulations in an ovary for two menstrual cycles may therefore provide improved conditions for the development of a healthier oocyte with an increased pregnancy potential.
Key words: anovulation in an ovary/corpus luteum/dominant follicle/pregnancy/two menstrual cycles
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Human follicular development from the preantral stage to the preovulatory follicle ready to undergo ovulation is estimated to take three menstrual cycles (Gougeon, 1986
, 1996). It is generally assumed that the follicle which is selected to ovulate from the responsive cohort of follicles in the early follicular phase contains a healthy fertilizable oocyte. However, the health of the oocyte from the dominant follicle is affected by the position of the dominant follicle and the corpus luteum from the previous cycle. When the dominant follicle develops contralateral to the ovary in which ovulation took place in the previous cycle, the follicular fluid contains a more favourable androgen to oestrogen ratio and the oocyte is more prone to undergo fertilization and pre-embryo development in vitro compared to when ovulations take place in one ovary in two consecutive cycles (Fukuda et al., 1996). A similar relationship was observed when a mild ovarian stimulation with clomiphene citrate (CC) was used (Fukuda et al., 1998). Collectively our previous studies suggest that the corpus luteum and/or the dominant follicle secrete factors which, at the local ovarian level, negatively affect the health of oocytes in the cohort of follicles recruited for the next menstrual cycle. A number of studies suggest a local antifolliculogenic effect of the corpus luteum (Goodman et al., 1977; Tyndale-Biscoe and Hawkins, 1977; diZerega and Hodgen 1981; Renfree et al., 1982; Tsuji et al., 1983; Fukuda et al., 1983, 1997a) and an influence of the dominant follicle on the neighbouring subordinate follicles during the late follicular phase (diZerega et al., 1982; Pache et al., 1990; Spears et al., 1996; Gore et al., 1997; Guet et al., 1997). It has been suggested that either progesterone, which is secreted in high concentrations by the corpus luteum during the luteal phase, or some unknown factors from the corpus luteum may be responsible for this local antifolliculogenic effect before the onset of the gonadotrophin-dependent follicular growth (Fukuda et al., 1980, 1983, 1997a). In order to study intra-ovarian factors affecting follicular and oocyte health we extended our previous studies and monitored three consecutive cycles. During all three cycles, the ovary from which follicular development, ovulation and corpus luteum formation took place was monitored by ultrasound. During the third cycle in-vitro fertilization (IVF) treatment was performed. The results from the IVF treatment were evaluated in relation to the position of follicular development, ovulation and corpus luteum formation during the previous two cycles.
|
Materials and methods |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
This study was performed between June 1990 and December 1997, and included women who were followed for three consecutive menstrual cycles. A total of 80 patients (mean age 29.4 ± 5.2, range 22–40) underwent a total of 270 IVF treatment cycles all showing unilateral ovulation. Forty-eight patients underwent 155 natural IVF cycles and 44 patients underwent 115 CC stimulated IVF cycles; 12 patients underwent both natural and CC stimulated IVF cycles. Causes of infertility were as follows: male factor, 70 couples; unknown, 10 couples. None of the patients received exogenous gonadotrophins for ovarian stimulation. Each of the women had two intact ovaries without ovarian cyst (i.e. persistent follicular cyst, chocolate cyst) and had shown pre-embryo development in at least one IVF attempt previously. None of the women had uterine abnormalities such as endometrial polyp, submucous myoma or synechia uteri assessed by transvaginal sonography, transvaginal hysterosonography (Fukuda et al., 1993
) or hysterosalpingography.
The treatment cycles were grouped into ovulation group (O) or anovulation group (A), according to whether ovulation or anovulation (no ovulation) was seen in the previous cycle in the same ovary as that with the dominant follicle during the treatment cycle. In group A ovulation was seen in the opposite ovary. Groups O and A were each further subdivided into two groups according to whether ovulation (O-) or anovulation (A-) was seen in the same ovary in the previous second cycle: O-O and A-O; O-A and A-A (previous second cycle-previous first cycle). Based on the IVF treatment of the third cycle, oocyte retrieval rate/total number of follicles, fertilization rate, cleavage rate (cleaved embryo/fertilized embryo), rate of pre-embryo formation/total number of follicles, pregnancy rate/cycle and implantation rate (clinical pregnancies/pre-embryo replaced) were assessed in each group. Clinical pregnancy was confirmed with gestational sac by transvaginal ultrasound. Only singleton pregnancies were observed in the present study except one monozygotic twin. Part of the material from the present study has been used in previous studies (Fukuda et al., 1995, 1996, 1998).
Natural IVF cycles
Follicular development of 48 patients with a history of regular menses (29.4 ± 3.1 days) was monitored daily by transvaginal ultrasound (SSA-250A Toshiba scanner with a 5.0 MHz convex vaginal probe or Sonovista CS or EX Mochida scanner with a 5.0, 6.0 or 7.5 MHz mechanical sector vaginal probe) from the time when the follicle measured 14 mm in diameter until oocyte retrieval. During the luteal phase (i.e. from day 5 of ovulation onwards) the site of corpus luteum was confirmed. Ovulation was predicted by the urinary luteinizing hormone (LH) surge (L-check: Nipro, Osaka or Gold Sign LH: Morinaga, Tokyo, Japan). Cycles with more than two preovulatory follicles were excluded from the natural cycles. All procedures were performed as described previously (Foulot et al., 1989; Fukuda and Fukuda, 1997b). In brief, human chorionic gonadotrophin (HCG) was given when the dominant follicle measured more than 18 mm in diameter and the oocyte was retrieved 34–35 h after HCG injection using transvaginal ultrasound guided follicle puncture and the follicle was flushed up to six times.
Clomiphene citrate IVF cycles
Forty-four patients received 50–150 mg/day of CC (Serophene®; Serono, Tokyo, Japan) from day 5 of the cycle for 5 days. The usual dose was 50 mg/day for 5 days and was only increased if ovarian response proved unsatisfactory in an earlier treatment cycle. The indications for administration of CC were as follows: (i) ovulation disorder, i.e. oligo-ovulation, anovulatory cycle; (ii) patients showing an endogenous LH surge with a dominant follicle of <17 mm in diameter during a natural IVF cycle. In CC cycles human chorionic gonadotrophin (HCG) was given when the leading follicle measured >20 mm in diameter. Preovulatory follicles measuring 14 mm or more were also aspirated and flushed up to six times. Bilateral ovulation cycles were excluded from the third cycles for IVF treatment in the present study.
Statistical evaluation was performed using 
2 test or Fisher's exact test. Differences were considered significant at P < 0.05. Results are presented as mean ±SD.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
IVF outcome in natural cycles
Results of the IVF treatment are given in Table I
. The oocyte retrieval rate/total number of follicles (92%), the fertilization rate (87%) and cleavage rate (88%) in group A were significantly higher than those of group O (73, 67 and 62% respectively). The rate of pre-embryo formation/total number of follicles (71%) in group A was significantly higher (P < 0.0001) than that of group O (30%). The pregnancy rate/cycle in group A (13%) was also higher, though not significantly (P = 0.07), than that of group O (5%). The implantation rates were similar (19 and 17% respectively).
|
The oocyte retrieval rate, the fertilization rate, the cleavage rate, the rate of pre-embryo formation were similar between A-A and O-A and also between A-O and O-O. However, the pregnancy rate seemed to increase from O-O through A-O and O-A to A-A (3, 6, 10 and 20%). The pregnancy rate in A-A (20%) was significantly (P < 0.05) higher than that of O-O (3%). The implantation rates in A-A (28%) and A-O (20%) were twice as high as those of O-A (14%) and O-O (11%) although the differences did not reach statistical significance.
IVF outcome in clomiphene citrate cycles
IVF outcomes in CC cycles are summarized in Table II. The oocyte retrieval rate/total number of follicles (88%) and fertilization rate (88%) in group A were significantly higher than those of group O (76 and 68% respectively). However, the cleavage rates were similar and high in both groups A (97%) and O (91%). The rate of pre-embryo formation/total number of follicles in group A (75%) was significantly (P < 0.0005) higher than that of group O (47%). As a result, the pregnancy rate/cycle in group A (28%) was significantly (P < 0.05) higher than that of group O (10%).
|
The oocyte retrieval rate and the fertilization rate in A-A (95 and 97%) were higher than those of O-A (81 and 77%), while these rates were similar in O-A and O-O. However, the cleavage rates during CC cycles were all high and similar among A-A, O-A, A-O and O-O, in contrast to those of natural cycles. The rate of pre-embryo formation in A-A (90%) was significantly (P < 0.005) higher than that of O-A (60%) despite there being no difference between A-O and O-O. The pregnancy rates increased from O-O through A-O and O-A to A-A (7, 14, 19 and 35%) as the number of previous ovulations in an ovary decreased. The pregnancy rate in A-A was significantly (P < 0.01) higher than that of O-O. The implantation rates in A-A (31%) and A-O (20%) were higher than those of O-A (19%) and O-O (10%) although the differences did not reach statistical significance.
IVF outcome in both natural cycles and clomiphene citrate cycles
IVF outcomes in natural cycles and CC cycles combined are summarized in Table III. The oocyte retrieval rate/total number of follicles (90%), the fertilization rate (87%), the cleavage rate (93%) and the rate of pre-embryo formation/total number of follicles (73%) in group A were significantly higher than those of group O (74, 68, 77 and 39% respectively). As a result the pregnancy rate/cycle in group A (20%) was also significantly (P < 0.005) higher than that of group O (7%).
|
The fertilization rate (95%) and the rate of pre-embryo formation (83%) in A-A were significantly (P < 0.02, P < 0.05) higher than those of O-A (81 and 66% respectively), while these rates were similar in A-O and O-O. The pregnancy rate in A-A (29%) was significantly higher than those of O-A (13%: P < 0.05), A-O (9%: P < 0.005) and O-O (5%: P < 0.001). The implantation rates in A-A (30%) and A-O (20%) were twice as high as those of O-A (16%) and O-O (10%) although the differences did not reach statistical significance. The rate of pre-embryo formation and the pregnancy rate increased from O-O through A-O and O-A to A-A as the number of previous ovulations in an ovary decreased, thus showing an inverse correlation with that of previous ovulations in an ovary (Table III
, Figure 1).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
The present study extends our previous studies (Fukuda et al., 1996
, 1998) and demonstrates for the first time that the health of the oocyte in the dominant follicle is affected by events in the ovary from which it develops during the two previous menstrual cycles. An ovary in which follicular development, ovulation and corpus luteum formation takes place apparently exerts local negative effects on the growing follicles. This negative effect is manifested not only one but two cycles later. It is expressed by a significantly decreased health and pregnancy potential of oocytes derived from dominant follicles developing in an ovary with three consecutive ovulations compared to an ovary which is ovulatory quiescent during the past two cycles. Thus, anovulations in an ovary during two consecutive cycles may provide conditions for the development of a healthier oocyte with an increased potential for conception. Oocytes from follicles developing in ovaries which experienced one cycle with ovulation and one without during the previous two cycles show a health and a pregnancy potential in between the above two groups. Taken together, the rate of pre-embryo formation and the pregnancy rate increase as the number of ovulations during the past two cycles decreases. The favourable health of oocytes from ovaries which were ovulatory inactive during the previous two cycles is obtained as a collective result of better rates of oocyte retrieval, fertilization, cleavage and pre-embryo development. Similar results are obtained in natural menstrual cycles and in CC stimulated cycles, and the effects are as a consequence clearly expressed when data from these two groups are combined.
If an oocyte experiences a local hostile environment caused by the development of a dominant follicle and/or the formation of a corpus luteum in an ovary, a permanent negative impact may be imposed on the oocyte, whereas the somatic cells of the follicle may, in response to gonadotrophin stimulation, regenerate health and enable them to acquire dominance in the follicular phase of a later cycle. Therefore, the present study does not question the generally accepted notion of the dominant follicle being selected during the late luteal phase and the early follicular phase of the menstrual cycle, but emphasizes that the oocyte of the selected follicle may not be the healthiest one present in the cohort of responsive follicles, and proposes that follicular and oocyte health may not inevitably be linked, i.e. the follicular cells may be healthy, whereas the oocyte of that follicle may not.
The implantation rates in A-A and A-O showing anovulation in an ovary two cycles previously seem to be twice as high as those of O-A and O-O. This may indicate that anovulation in the previous second cycle not only improves oocyte health but also causes a better quality corpus luteum secreting steroid hormones appropriate for implantation and optimal uterine receptivity.
The results of the present study together with our previous studies (Fukuda et al., 1996, 1998) may reflect that progesterone or the corpus luteum exerts a local paracrine antifolliculogenic effects on follicles before they reach gonadotrophin-dependent follicular growth. Progesterone has been shown to have such an antifolliculogenic effect (Moore and Greenwald, 1974; Mizuno et al., 1976; Akahori, 1978; Fukuda et al., 1980; Schreiber et al., 1980, 1981, 1982; Tyler et al., 1980). Progesterone may inhibit follicle-stimulating hormone (FSH)-stimulated granulosa oestrogen production (Schreiber et al., 1980, 1981, 1982) through a progesterone-binding protein with receptor like features located on the surface of granulosa cells (Peluso and Pappalardo, 1998).
A number of studies are in agreement with the present study: Lass et al. (1997) showed poor ovulation responses in women with a single ovary and a lower IVF pregnancy rate was observed in women with only one ovary (17%) compared to those with two ovaries (28%) (Khalifa et al., 1992). The decreased conception rate of women with one ovary may reflect that continuous ovulations produce suboptimal oocytes.
Sackoff et al. (1994) indicated that women who conceived within the first ovulation or even the second ovulation after termination of taking oral contraceptives had a lower risk of chromosomally normal spontaneous abortions, supporting the observations of the present study. Moreover, a previous work showed that down-regulation with luteinizing hormone-releasing hormone agonists for 3–4 months improves implantation rates (Edwards, 1996). Reports have also shown that induced anovulation using oral contraceptives prior to ovarian stimulation with gonadotrophins improves IVF and pregnancy outcome (Fisch et al., 1996; Damario et al., 1997). These studies are also in agreement with the present data and our previous studies (Fukuda et al., 1996, 1998) showing that a previous ovulatory quiescent ovary favours pregnancy. Therefore, anovulation using oral contraceptives prior to CC–IVF treatment may offer a milder form of ovarian stimulation as proposed by Edwards et al. (1997).
Women in the general population without any known fertility problem who seek to achieve a pregnancy experience a conception rate of around 25–30% per cycle. This is surprisingly low and ranks humans as poor breeders compared to other species. While a number of factors undoubtedly contribute to the low fertility of humans, the present study demonstrates a mechanism which may reduce the natural occurring fertility of humans. It will be of interest to evaluate whether other single ovulatory species like the large domestic animals show a similar pattern affecting the health of the oocyte contained in the dominant follicle.
In conclusion, the health of the oocyte from the dominant follicle seems to be affected by local ovarian conditions earlier, up to two menstrual cycles, than previously shown. The presence of a corpus luteum and/or a dominant follicle is likely to exert unfavourable local effects on the oocyte contained in the follicle which may subsequently be selected to ovulate one or two cycles later. Anovulations in an ovary (an ovulatory quiescent ovary) during two menstrual cycles provide improved conditions for the development of a healthier oocyte with an increased pregnancy potential. This study strongly proposes clinical application of anovulation using oral contraceptives prior to IVF treatment.
|
Notes |
|---|
3 To whom correspondence should be addressed
|
References |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Akahori, T. (1978) The effect of follicular maturation and sex steroids upon LH and FSH binding to porcine granulosa cells. Acta Obstet. Gynaecol. Jpn, 30, 191–198.
Damario, M.A., Barmat, L., Liu, H-C. et al. (1997) Dual suppression with oral contraceptives and gonadotrophin releasing-hormone agonists improves in-vitro fertilization outcome in high responder patients. Hum. Reprod., 12, 2359–2365.
diZerega, G.S. and Hodgen, G.D. (1981) Folliculogenesis in the primate ovarian cycle. Endocr. Rev., 2, 27–49.
diZerega, G.S., Goebelsmann, U. and Nakamura, R.M. (1982) Identification of protein(s) secreted by the preovulatory ovary which suppresses the follicle response to gonadotropins. J. Clin. Endocrinol. Metab., 54, 1091–1096.
Edwards, R.G. (1996) Human conception in vitro, 1995, a summing up. Hum. Reprod., 11 (suppl. 1), 199–211.
Edwards, R.G., Lobo, R.A. and Bouchard, P. (1997) Why delay the obvious need for milder forms of ovarian stimulation? Hum. Reprod., 12, 399–401.[Web of Science][Medline]
Fisch, B., Royburt, M., Pinkas, H. et al. (1996) Augmentation of low ovarian response to superovulation before in vitro fertilization following priming with contraceptive pills. Isr. J. Med. Sci., 32, 1172–1176.[Web of Science][Medline]
Foulot, H., Ranoux, C., Dubuisson, J.B. et al. (1989) In vitro fertilization without ovarian stimulation: A simplified protocol applied in 80 cycles. Fertil. Steril., 52, 617–621.[Web of Science][Medline]
Fukuda, M., Katayama, K. and Tojo, S. (1980) Inhibitory effect of progesterone on follicular growth and induced superovulation in the rat. Arch. Gynecol., 230, 77–87.[Web of Science][Medline]
Fukuda, M., Katayama, K., Tsujimoto, D. et al. (1983) Inhibitory effect of corpus luteum on follicular growth and induced superovulation in immature rats. Jpn J. Fertil. Steril., 28, 45–49.
Fukuda, M., Shimizu, T., Fukuda, K. et al. (1993) Transvaginal hysterosonography for differential diagnosis between submucous and intramural myoma. Gynecol. Obstet. Invest., 35, 236–239.[Web of Science][Medline]
Fukuda, M., Fukuda, K., Yding Andersen, C. and Byskov, A.G. (1995) Healthy and atretic follicles: vaginosonographic detection and follicular fluid hormone profiles. Hum. Reprod., 10, 1633–1637.
Fukuda, M., Fukuda, K., Yding Andersen, C. and Byskov, A.G. (1996) Contralateral selection of dominant follicle favours pre-embryo development. Hum. Reprod., 11, 1958–1962.
Fukuda, M., Fukuda, K., Yding Andersen, C. and Byskov, A.G. (1997a) Does corpus luteum locally affect follicular growth negatively? Hum. Reprod., 12, 1024–1027.
Fukuda, M. and Fukuda, K. (1997b) A simplified in-vitro fertilization (IVF) using disposable materials. Hum. Reprod., 12, 2588–2590.[Web of Science][Medline]
Fukuda, M., Fukuda, K., Yding Andersen, C. and Byskov, A.G. (1998) Contralateral ovulation shortens follicular phase length and favours pre-embryo development during ovarian stimulation with clomiphene citrate. Hum. Reprod., 13, 1590–1594.
Goodman, A.L., Nixon, W.E., Johnson, D.K. and Hodgen, G.D. (1977) Regulation of folliculogenesis in the cycling rhesus monkey: selection of dominant follicle. Endocrinology, 100, 155–161.
Gore, M.A., Nayudu, P.L. and Vlaisavljevic, V. (1997) Attaining dominance in vivo: distinguishing dominant from challenger follicles in humans. Hum. Reprod., 12, 2741–2747.
Gougeon, A. (1986) Dynamics of follicular growth in the human: a model frompreliminary results. Hum. Reprod., 1, 81–87.
Gougeon, A. (1996) Regulation of ovarian follicular development in primates: facts and hypothesis. Endocr. Rev., 17, 121–155.
Guet, P., Driancourt, M.A., Paris, A. et al. (1997) Inhibitory effect of dominant follicular fluid on human granulosa cells: a revisited hypothesis. Hum. Reprod., 12, (Abstract Book 1), 199.[Web of Science][Medline]
Khalifa, E., Toner, J.P., Muasher, S.J. and Acosta, A.A. (1992) Significance of basal follicle-stimulating hormone levels in women with one ovary in a program of in vitro fertilization. Fertil. Steril., 57, 835–839.[Web of Science][Medline]
Lass, A., Paul, M.E., Margara, R. and Winston, R.M.L. (1997) Women with one ovary have decreased response to GnRHa/HMG ovulation induction protocol in IVF but the same pregnancy rate as women with two ovaries. Hum. Reprod., 12, 298–300.
Mizuno, T., Wada, H., Nakano, R. et al. (1976) Effects of estrogen and progesterone on follicular growth in hypophysectomized rats. Folia Endocrinology Jpn, 52, 372 (abst 213 in Japanese).
Moore, P.J. and Greenwald, G.S. (1974) Effect of hypophysectomy and gonadotropin treatment on follicular development and ovulation in the hamster. Am. J. Anat., 139, 37–38.[Web of Science][Medline]
Pache, T.D., Wladimiroff, J.W., de Jong, F.H. et al. (1990) Growth patterns of nondominant ovarian follicles during the normal menstrual cycle. Fertil. Steril., 54, 638–642.[Web of Science][Medline]
Peluso, J.J. and Pappalardo A. (1998) Progesterone mediates its anti-mitotic and anti-apoptotic actions in rat granulosa cells through a progesterone-binding protein with gamma aminobutyric acid receptor-like features. Biol. Reprod., 58, 1131–1137.
Renfree, M.B., Wallace, G.I. and Young, I.R. (1982) Effects progesterone, oestradiol-17B and androstenedione on follicular growth after removal of the corpus luteum during lactational and seasonal quiescence in the Tammar Wallaby. J. Endocrinol., 92, 397–403.
Sackoff, J., Kline, J. and Susser, M. (1994) Previous use of oral contraceptives and spontaneous abortion. Epidemiology, 5, 422–428.[Web of Science][Medline]
Schreiber, J.R., Nakamura, K. and Erickson, G.F. (1980) Progestins inhibit FSH-stimulated steroidogenesis in cultured rat granulosa cells. Mol. Cell. Endocrinol., 19, 165–173.[Web of Science][Medline]
Schreiber, J.R., Nakamura, K. and Erickson, G.F. (1981) Progestins inhibit FSH-stimulated granulosa estrogen production at a post-cAMP site. Mol. Cell. Endocrinol., 21, 161–170.[Web of Science][Medline]
Schreiber, J.R., Nakamura, K. and Erickson, G.F. (1982) Progestins inhibit FSH-induced functional LH receptors in cultured rat granulosa cells. Mol. Cell. Endocrinol., 25, 113–124.[Web of Science][Medline]
Spears, N., de Bruin, J.P. and Gosden, R.G. (1996) The establishment of follicular dominance in co-cultured mouse ovarian follicles. J. Reprod. Fertil., 106, 1–6.
Tsuji, K., Sowa, M. and Nakano, R. (1983) Relationship among the status of the human oocyte, the 17B-estradiol concentration in the antral fluid and the follicular size. Endocrinol. Japon., 30, 251–254.[Medline]
Tyler, J.P.P., Smith, D.M. and Biggers, J.D. (1980) Effect of steroids on oocyte maturation and atresia in mouse ovarian fragments in vitro. J. Reprod. Fertil., 58, 203–212.
Tyndale-Biscoe, C.H. and Hawkins, J. (1977) The corpora lutea of marsupials: aspects of function and control. In Calaby, J.H. and Tyndale-Biscoe, C.H. (eds) Reproduction and evolution. Australian Academy of Science, Canberra, pp. 245–252.
Submitted on June 12, 1998; accepted on October 14, 1998.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Fukuda, K. Fukuda, C. Y. Andersen, and A. G. Byskov Characteristics of human ovulation in natural cycles correlated with age and achievement of pregnancy Hum. Reprod., December 1, 2001; 16(12): 2501 - 2507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fukuda, K. Fukuda, C. Y. Andersen, and A. G. Byskov Right-sided ovulation favours pregnancy more than left-sided ovulation Hum. Reprod., September 1, 2000; 15(9): 1921 - 1926. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||