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PubMed1995

Late intracytoplasmic sperm injection in unexpected failed fertilization in vitro: diagnostic or therapeutic?

OBJECTIVE: To evaluate fertilization potential of 24-hour-old unfertilized oocytes using intracytoplasmic sperm injection and the pregnancy potential of resultant embryos. DESIGN: Prospective observational study. SETTING: Private infertility clinic, London, United Kingdom. PATIENTS: Fifteen patients with a history of infertility who underwent treatment with IVF and showed failure of fertilization on the day after oocyte retrieval. INTERVENTION: Assisted fertilization with intracytoplasmic sperm injection was carried out at 24 hours after oocyte retrieval. RESULTS: A total of 121 metaphase II oocytes were subjected to intracytoplasmic sperm injection. Of these, 9 were damaged (7%), 2 were polyploidic (2%), and 58 showed normal fertilization (48%). Of the latter, 47 cleaved normally (81%). Forty embryos were transferred and three were cryopreserved. One patient conceived (7%) but in this case only one of three embryos transferred was from intracytoplasmic sperm injection. CONCLUSION: Late (24 hours) intracytoplasmic sperm injection can give good fertilization and cleavage rates but the potential of the generated embryos to achieve pregnancy seems to be low.

Adult↗
PubMed2004

[Delivery after cryopreservation of percutaneous epididymal sperm aspiration specimens and intracytoplasmic sperm injection: 1 case report].

Intracytoplasmic sperm injection (ICSI) with sperm collected by percutaneous epididymal sperm aspiration (PESA) technique is nowadays the main treatment for obstructive azoospermia(OAS). To cryopreserve the epididymal sperm obstained by PESA can avoid repeat retrievals. We transferred the embryos fertilized by ICSI with frozen/thawed epididymal sperm and achieved a delivery, which shows that epididymal sperm obstained by PESA can be successfully cryopreserved.

Adult↗
PubMed2005

Expression of mRNA and protein of macrophage colony-stimulating factor and its receptor in human follicular luteinized granulosa cells.

OBJECTIVE: To evaluate the concentration of macrophage colony-stimulating factor (M-CSF) in serum and follicular fluid (FF) at the time of oocyte retrieval and to detect expression of M-CSF and its receptor by luteinized granulosa cells (GCs). DESIGN: Collection of serum and FF at the time of oocyte retrieval. SETTING: A university IVF- intracytoplasmic sperm injection (ICSI) program. PATIENT(S): Serum and FF were obtained from 85 women undergoing oocyte retrieval. INTERVENTION(S): Serum and FF were obtained from 85 women. The GCs were pooled from 15 (3 x 5) patients (3-14 oocytes each). MAIN OUTCOME MEASURE(S): The M-CSF concentration was determined by ELISA, the expression of M-CSF and its receptor by the immunocytochemical technique and reverse transcription polymerase chain reaction analysis. In addition, M-CSF expression was investigated by cell culture time course studies. RESULTS: The median M-CSF concentration in FF (2,409.2 pg/mL) was significantly higher than that in serum (242.5 pg/mL). The M-CSF and its receptor were expressed by GCs. CONCLUSION(S): The significantly higher level of M-CSF in FF than in serum and the expression of M-CSF and its receptor in FF by GCs suggest an important role for this growth factor in ovarian function.

Embryo Transfer↗
PubMed1997

Morphometry of normal and teratozoospermic canine sperm heads using an image analyzer: work in progress.

Combining the traditional morphologic evaluation of spermatozoa with computer assisted image analysis adds randomness, objectivity, repeatability and accuracy to morphometric measurements. We collected semen from 10 fertile, normospermic dogs aged 1 to 7 yr and from 3 teratozoospermic breed-matched dogs. Sperm head morphology was examined in Giemsa-stained smears by light microscopy, using a computer-assisted image analyzer and by transmission electron microscopy. We found significant variation in sperm head area, length, width and degree of roundness among normospermic individual dogs, indicating that it would be necessary to examine many more dogs before the size and shape of normal dog spermatozoa could be determined. The normospermic dogs were used as controls for the teratozoospermic cases. Case 1: A 2-yr-old subfertile Cavalier King Charles Spaniel had semen with small and narrow-based sperm heads and a proximal cytoplasmic droplet in most of the spermatozoa. With the image analysis system, sperm heads were shown to be smaller and more oval than in normospermic dogs. The variatons in size and shape were similar in magnitude to those of control dogs. An examined infertile half-brother had similar semen quality. Case 2: A 3-yr-old Petit Basset Griffon Vendeen with 2 unsuccesfull matings exhibited spermatozoa with severe abnormalities. Measured by image analyzer, sperm heads were irregular in shape and very small in area. One of the two littermates examined had semen of the same quality as the case dog. Case 3: A 3-yr-old fertile Golden Retriever had semen with giant sperm heads in about 50% of spermatozoa. Image analyzing results revealed 2 populations of different sized sperm heads. Giant heads consisted of 52.2% of all spermatozoa. The results of the study reported here suggest that the image analysis technique may be useful in evaluating structural changes in sperm morphology, supplementing visual assessment that is used in conventional methods.

Journal Article↗
PubMed1997

Teratozoospermia influences fertilization rate in vitro but not embryo quality.

The purpose of this study was to retrospectively compare the overall results and embryo quality in 102 cycles of in-vitro fertilization (IVF)-embryo transfer using normal frozen donor semen (group D) and 94 cycles of IVF-embryo transfer using husbands' teratozoospermic sperm (group T). Donor semen was purchased from men with proven fertility and normal semen parameters. Teratozoospermia was defined in group T as the presence of <20% of normal spermatozoa in semen on the day of oocyte retrieval. Exclusion criteria were a sperm count <10 x 10(6)/ml or with <10% progressive motility. Fertilization rate, transfer rate and number of transferred embryos per cycle were significantly lower in the teratozoospermic group (45 vs 72%, 66 vs 96%, 1.7 vs 2.9%, respectively). Pregnancy rate per cycle was also lower, but not significantly (18 vs 28%). However, pregnancy rate per transfer, implantation rate per transferred embryo and take home baby rate were comparable (27 vs 30%, 15 vs 15%, 21 vs 24%, respectively). Similarly, embryo quality in terms of number of embryos displaying fragmentations or irregular cells, cleavage stages and embryo scores were comparable. When group T was divided into two subgroups according to sperm count (group T1: sperm count = 10-20 x 10(6)/ml; group T2: sperm count >20 x 10(6)/ml), there was no difference between them with regard to fertilization rate, pregnancy rate or embryo quality. This study confirms low pregnancy rate per cycle in IVF-embryo transfer using teratozoospermic semen, but demonstrates for the first time that embryo quality and viability are not impaired. It is proposed that the poor pregnancy rate per cycle obtained is due only to the poor fertilization rate, and to the subsequent limited choice of embryos to be transferred.

Cryopreservation↗
PubMed1999

No transfer in a planned ICSI cycle: we cannot overcome some basic rules of human reproduction.

Since intracytoplasmic sperm injection (ICSI) has been introduced in the techniques for the non-causal treatment of severe male factor infertility failure of conventional in-vitro fertilisation and subsequent embryo transfer due to failed oocyte-fertilisation has become rare in these cases. Nonetheless, even in ICSI cycles cases occur where no transfer can be performed for several reasons. The contribution of sperm-, oocyte- and other factors are reviewed in this article. 78 (5.4%) out of 1433 ICSI cycles, performed from 1.1.1995 up to 31.5.1997, in which no transfer could be done, despite a performed follicular puncture, were used as an example. 30 cycles with no fertilisation, 17 with no oocytes, 8 with only degenerated oocytes retrieved, 17 with no injectable sperms, 4 with no normal fertilisation, and 2 with no cleavage after normal fertilisation were identified. In more than two thirds of the cases an oocyte factor, identified by a high FSH, low response to the hormonal stimulation or no fertilization despite the presence of motile sperms, was present. The other cases were attributed to a sperm factor or other causes. After one failed ICSI cycle - i.e. a cycle with no embryo transfer - the chance to conceive is very low in a subsequent cycle. Only 1 out of 24 cycles was successful in terms of an established and ongoing pregnancy.

Adult↗
PubMed1998

Management of transient ovarian failure: pregnancy after in vitro fertilization and intracytoplasmic sperm injection--a case report.

PURPOSE: The case history of a 36-year-old patient with transient ovarian failure, presumably induced by previous ovarian surgery and a recent pelvic inflammatory disease, is described. METHODS: During several months, the patient underwent transvaginal ultrasound and hormonal follow-up. Ovulation was triggered by hCG in a cycle in which spontaneous follicular ripening had occurred. Transvaginal puncture of the single follicle was performed for in vitro fertilization. RESULTS: One oocyte was retrieved and fertilized by intracytoplasmic sperm injection, giving rise to a single good-quality embryo. A singleton pregnancy, which ended in the birth of a healthy daughter, was established. CONCLUSIONS: This case demonstrates that it is worthwhile to monitor patients with transient ovarian failure closely, and if other infertility factors are present, IVF of one oocyte may be considered.

Adult↗
PubMed2000

Factors associated with the formation of triploid zygotes after intracytoplasmic sperm injection.

OBJECTIVE: To determine whether clinical or laboratory factors influence development of triploid (3PN) zygotes after ICSI. DESIGN: Retrospective review. SETTING: The assisted reproductive technology program of Brigham and Women's Hospital. PATIENT(S): Patients undergoing ICSI. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cycles were divided into two groups: group A, cycles with one or more 3PN zygotes after ICSI, and group B, cycles with no 3PN zygotes. Age, amount of gonadotropin administered, peak estradiol levels, number of follicles, number of oocytes retrieved and injected, time between retrieval and injection, oocyte abnormalities, sperm type and motile count, percentage of diploid zygotes, and ongoing pregnancy rates were compared between groups. RESULT(S): Compared with patients in group B, those in group A received fewer ampoules of gonadotropins, had higher estradiol levels, and had more follicles on the day of hCG administration, oocytes, immature oocytes and oocytes injected and lower percentages of diploid zygotes. However, ongoing pregnancy rates did not differ between groups. CONCLUSION(S): Patients who produce 3PN zygotes after ICSI are high responders to ovarian stimulation. The appearance of such embryos is not associated with lower ongoing pregnancy rates and should not necessarily dictate alterations in ovarian stimulation protocols.

Adult↗
PubMed2006

Effect of an oral contraceptive pill on follicular development in IVF/ICSI patients receiving a GnRH antagonist: a randomized study.

This randomized controlled study compared the effectiveness of a gonadotrophin releasing hormone (GnRH) antagonist protocol with or without oral contraceptive (OC) pretreatment on the number of oocytes retrieved in IVF or intracytoplasmic sperm injection (ICSI) patients. Sixty-four patients were randomized to start recombinant human FSH (r-hFSH) on day 2 or 3 after OC withdrawal (OC group) or on day 2 of a natural cycle (control group). From stimulation day 6 onwards, all patients were treated with daily (0.5 mg/ml) GnRH antagonist (Antide). OC pretreatment resulted in significantly lower starting concentrations of FSH, LH and oestradiol (P < 0.001) and a thinner endometrium (P < 0.0001). In the early stimulation period, fewer large follicles were found after OC pretreatment, leading to a significantly extended stimulation period (11.6 versus 8.7 days, P < 0.0001) with more follicles on the day of recombinant human chorionic gonadotrophin administration (15.4 versus 12.5, P = 0.02) and more oocytes retrieved (13.5 versus 10.2, P < 0.001) as compared with the control group. GnRH antagonist regimen, pretreated with OC, prevented the early endogenous FSH rise and improved follicular homogeneity, resulting in more oocytes. As a consequence of the extended treatment period, more rhFSH was required.

Adult↗
PubMed2004

The outcome of ICSI of immature MI oocytes and rescued in vitro matured MII oocytes.

BACKGROUND: The use of immature oocytes is limited to cases where these are the only available oocytes, and they are usually only microinjected with sperm after having undergone maturation in vitro. This study compares the outcome of injection of sperm into metaphase I oocytes immediately after their denudation (MI) performed 2 h after their retrieval, with the outcome of injection of sperm into rescued in vitro matured metaphase II (IVM MII) oocytes after their short incubation in routine laboratory conditions. METHODS: ICSI was performed on MI oocytes, rescued IVM MII oocytes and on MI oocytes that were incubated but failed to extrude their first polar body (arrested IVM MI). Fertilization and cleavage rates were compared with those achieved in mature metaphase II oocytes (MII). RESULTS: ICSI of MI oocytes showed impaired performance compared with ICSI of rescued IVM MII oocytes and MII oocytes, in terms of oocyte degeneration rate (11 versus 6 versus 4%; P < 0.0001), fertilization rate (28 versus 44 versus 68%; P < 0.0001) and multipronucleated fertilization (10 versus 4 versus 4%; P < 0.01). The cleavage rate was lower in rescued IVM MII oocytes compared with MII oocytes (86 versus 95%; P < 0.01). Arrested IVM MI oocytes showed similar results to those of MI oocytes but had a lower cleavage rate (72 versus 96%; P < 0.01). CONCLUSIONS: The injection of rescued IVM MII oocytes is preferred to the injection of MI oocytes.

Adult↗
PubMed2001

Benefit of FSH priming of women with PCOS to the in vitro maturation procedure and the outcome: a randomized prospective study.

The aim of this study was to determine whether the rates of in vitro oocyte maturation, fertilization and cleavage, as well as implantation rate and pregnancy rate, could be improved by low-dose priming with FSH in vivo before retrieval of immature oocytes in patients with polycystic ovary syndrome (PCOS). From March 1998 to June 2000, a total of 28 women underwent 36 completed treatment cycles, randomized sequentially in one of two groups. Women in group 1 (n = 12 cycles) received no stimulation and women in group 2 (n = 24 cycles) received 150 iu recombinant FSH day(-1) for 3 days, initiated on day 3 after menstruation. Aspiration was performed transvaginally between day 9 and day 17 in the unstimulated group and on day 8 or day 9 in the FSH-primed group after FSH deprivation for 2 or 3 days. All cumulus-enclosed oocytes of healthy appearance were matured in culture medium (TCM-199) in vitro for 28-36 h before intracytoplasmic sperm injection (ICSI). After oocyte retrieval the women were given oestradiol (6 mg day(-1)) and progesterone administration (300 mg day(-1)) was initiated 2 days later. Suitable embryos (maximum two embryos) were transferred on day 3 after ICSI. The percentage of oocytes reaching metaphase II was significantly higher (P < 0.05) in the FSH-primed group (59%, 92/156) compared with the non-primed group (44%, 36/81). There were no significant differences in the rates of oocyte fertilization and cleavage between these groups. No pregnancies were obtained in group 1 (0%, 0/12), whereas seven clinical pregnancies were obtained in group 2 (29%, 7/24) (P < 0.05). In group 2, 37 embryo transfers resulted in eight implantations (21.6%). Three healthy singleton children have been born at term; the remaining pregnancies ended with spontaneous abortions in the first trimester. These results indicate that priming with recombinant FSH before harvesting of immature oocytes from patients with PCOS may improve the maturational potential of the oocytes and the implantation rate of the cleaved embryos.

Adult↗
PubMed1996

Successful combination of transrectal electroejaculation and intracytoplasmic sperm injection in the treatment of anejaculation.

We describe the case of a couple whose infertility was caused by the absence of seminal emission following retroperitoneal surgery for testicular cancer. Ejaculate could be retrieved from the husband by rectal probe electroejaculation (RPE) but sperm quality was so poor that conventional in-vitro fertilization was impossible. With intracytoplasmic sperm injection of spermatozoa retrieved by RPE - a combination not reported previously - we were able to induce a pregnancy with successful outcome.

Adult↗
PubMed1987

An increase in in vitro fertilization ability of low-density human sperm capacitated by multiple-tube swim-up.

Comparison was made of the efficacy of multiple-tube swim-up (MT-SU) and single-tube swim-up (ST-SU) preparations on inducing human sperm fertilization ability in semen samples of less than 60 million motile sperm/ml. Two parallel groups of in vitro fertilization (IVF) patients possessing sperm density of this category had their sperm capacitated by MT-SU or ST-SU. The MT-SU patients' sperm fertilized 71 +/- 6.0% of eggs retrieved in comparison to 39 +/- 7.9% in the parallel ST-SU patients (P less than 0.001). Similarly, MT-SU increased the rate of human sperm penetration into zona-free hamster eggs. The increased fertilization rate of MT-SU sperm was not from acceleration of the acrosome reaction, but may be attributed to the higher efficiency of MT-SU in removing antifertility factors present in the seminal plasma from sperm.

Acrosome↗
PubMed2003

Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment.

Replacing GnRH agonist cotreatment for the prevention of a premature rise in LH during ovarian stimulation for in vitro fertilization (IVF) by the late follicular phase administration of GnRH antagonist may render supplementation of the luteal phase redundant, because of the known rapid recovery of pituitary function after antagonist cessation. This randomized two-center study was performed to compare nonsupplemented luteal phase characteristics after three different strategies for inducing final oocyte maturation. Forty patients underwent ovarian stimulation using recombinant (r-)FSH (150 IU/d, fixed) combined with a GnRH antagonist (antide; 1 mg/d) during the late follicular phase. When at least one follicle above 18 mm was observed, patients were randomized to induce oocyte maturation by a single injection of either r-human (h)CG (250 microg) (n = 11), r-LH (1 mg) (n = 13), or GnRH agonist (triptorelin; 0.2 mg) (n = 15). Retrieved oocytes were fertilized by either IVF or intracytoplasmatic sperm injection, depending on sperm quality. Embryo transfer was performed 3-4 d after oocyte retrieval. No luteal support was provided. Serum concentrations of FSH, LH, estradiol (E(2)), progesterone (P), and hCG were assessed at fixed intervals during the follicular and luteal phase. The median duration of the luteal phase was 13, 10, and 9 d for the r-hCG, the r-LH, and the GnRH agonist group, respectively (P = 0.005). The median area under the curve per day (from 4 d post randomization until the onset of menses) for LH was 0.50, 2.34, and 1.07 for the r-hCG, the r-LH, and the GnRH agonist group, respectively (P = 0.001). The median area under the curve per day for P was 269 vs. 41 and 16 for the r-hCG, the r-LH, and the GnRH agonist group, respectively (P < 0.001). Low pregnancy rates (overall, 7.5%; range, 0-18% per started cycle) were observed in all groups. In conclusion, the nonsupplemented luteal phase was insufficient in all three groups. In the patients receiving r-hCG, the luteal phase was less disturbed, compared with both other groups, presumably because of prolonged clearance of hCG from the circulation and the resulting extended support of the corpus luteum. Despite high P and E(2) concentrations during the early luteal phase in all three groups, luteolysis started prematurely, presumably because of excessive negative steroid feedback resulting in suppressed pituitary LH release. Hence, support of corpus luteum function remains mandatory after ovarian stimulation for IVF with GnRH antagonist cotreatment.

Adult↗
PubMed1993

The hemizona assay: its role in identifying male factor infertility in assisted reproduction.

OBJECTIVES: To identify male factor infertility among a group of patients in an assisted reproductive program (phase 1) and to evaluate the hemizona assay (HZA) in the diagnosis and prognosis of such a program (phase 2). DESIGN: The IVF performance of normal gametes in the Tygerberg program were critically evaluated. Female patients were classified as pure tubal factor infertility, having a normal FSH:LH ratio on day 3 of the menstrual cycle. All participating women produced three or more preovulatory oocytes at retrieval and were inseminated with sperm considered normal by all present diagnostic criteria. The total and normal fertilization rate thresholds were defined in that group. Using those thresholds, couples tested for sperm binding in the HZA (n = 48) were used and divided into two groups according to their fertilization rates, namely group 1, low fertilization (< 55%) and group 2, normal fertilization (> 55%). SETTING: University-based tertiary care center. PATIENTS: Ninety-nine couples (589 oocytes) with pure tubal factor infertility and normal male factor were used in phase 1. Forty-eight couples with normal and abnormal male factors that had both HZA performed and IVF treatment were included in phase 2. RESULTS: Investigation of the performance of normal gametes in 99 couples (589 oocytes) revealed the total fertilization rate (total number of oocytes fertilized/total number of oocytes inseminated) was (mean +/- SD) 88.6% +/- 16.8% and the normal fertilization rate (total number of oocytes with normal fertilization/total number of oocytes inseminated) was 81.3% +/- 22%. The minimum total fertilization rate that can be considered normal in the Tygerberg program using mean--2 SD is therefore 55% and for normal fertilization rate is 37%. The group with low fertilization rate (< 55%) showed a mean hemizona index (HZI) significantly lower; nevertheless, the distribution overlapping indicates a low discriminating power of the HZA. A sensitivity of 75% and a specificity of 75% were found; the positive and negative predictive values were 81% and 68%, respectively. CONCLUSIONS: The results indicated the HZA and HZI contribute important information and can serve in conjunction with other semen characteristics as useful tools during the diagnosis of the male factor in assisted reproduction.

Chorionic Gonadotropin↗
PubMed2002

Blastocyst culture in human IVF: the final destination or a stop along the way?

In the field of human IVF, culturing embryos to the blastocyst stage has gained popularity within the past few years. The impetus to transfer blastocysts has been spurred by several factors: 1) the desire to improve implantation rates in infertility patients, 2) a desire to reduce the multiple pregnancy rate by transferring fewer embryos, 3) the desire to perform pre-implantation genetic diagnosis, and 4) the advent of sequential media. Although culturing human embryos to the Hastocyst stage has improved implantation rates and reduced the incidence of multiple pregnancies in some patient populations, it has not worked for all populations of infertility patients. Factors that may affect the ability of a human embryo to reach the blastocyst stage include the patient's age, cohort of ova retrieved, the use of intracytoplasmic sperm injection of blastomere biopsy, culture conditions, or intrinsic factors within the embryo itself. Culture of human embryos to the blastocyst stage can be an effective method for improving implantation rates and reducing the high order multiple pregnancy rates seen in human IVF clinics when more than three embryos are transferred.

Adult↗
PubMed2005

Factors predicting IVF treatment outcome: a multivariate analysis of 5310 cycles.

The objective of this study was to analyse factors predicting live birth rate following IVF. A computerized database of 1928 women who underwent 5310 consecutive IVF cycles in a single IVF unit was evaluated. Data on the women's age, number of retrieved oocytes, performance of intracytoplasmic sperm injection (ICSI), aetiology of infertility, number of transferred embryos and option of choosing embryos for transfer were evaluated. There were 1126 pregnancies that resulted in 689 live births. Transferring two embryos doubled the chances of delivery compared with one embryo, but transferring three embryos was not significantly superior to two embryos. Moreover, following a three-embryo transfer, the multiple delivery rates were significantly higher (P < 0.01) compared with transferring two embryos. Optimal delivery rates were observed in women aged 26-30 years, with gradual decline with advanced age. The performance of ICSI resulted in higher delivery rates compared with conventional insemination. According to these data, the best live birth results following IVF treatment were achieved when the maternal age was 26-30 years, in couples with male factor infertility undergoing ICSI, and when two embryos were transferred.

Adolescent↗
PubMed1998

Preimplantation genetic diagnosis of inherited cancer: familial adenomatous polyposis coli.

PURPOSE: Our purpose was to achieve preimplantation genetic diagnosis (PGD) of the dominant cancer predisposition syndrome, familial adenomatous polyposis coli (FAPC), as an alternative to prenatal diagnosis. METHODS: The affected patient was superovulated and oocytes were retrieved and fertilized by intracytoplasmic sperm injection (ICSI). Two cells were biopsied from each embryo and the whole genome was amplified by primer extension preamplification (PEP). Nested PCR was then used to amplify two APC fragments: one including the APC mutation site and the other an informative intragenic polymorphism. Both were detected by simultaneous single-strand conformation polymorphism and heteroduplex analysis. RESULTS: Four normally fertilized embryos were biopsied on day 3 post ICSI, and two cells were successfully removed from each embryo. Following PEP the APC mutation was successfully amplified in 7 of 8 cells, and the polymorphism in 6 of 8 cells. The APC mutation was detected in three embryos. This result was confirmed by identification of the mutation associated polymorphism in two cases. A single embryo was diagnosed as homozygous normal for the mutation and the polymorphism in both cells sampled. This unaffected embryo was transferred to the mother, but no pregnancy resulted. CONCLUSIONS: We report here the first diagnosis of a cancer predisposition syndrome in human preimplantation embryos. Our results indicate that difficulties associated with single-cell PCR, allele-specific amplification failure in particular, need not prevent preimplantation diagnosis of diseases with a dominant mode of inheritance, provided appropriate strategies are applied.

Adenomatous Polyposis Coli↗