Savior Siblings and More

2. Savior Siblings and More • Innovative ways to conceive offspring: • 1) Couple in search of an oocyte donor advertises for an attractive, athletic woman • 2) Cancer patient stores her oocytes before therapy; becomes a mother two years later • 3) A paralyzed man has sperm removed and injected into his partner’s oocyte

3. Savior Siblings and More Lisa and Jack Nash sought to have a child for a different reason They conceived and selected Adam to save his sister’s life - She was suffering from Fanconi anemia A month after his birth, physicians infused Adam’ umbilical cord stem cells into Molly

4. Adam and Molly Nash Figure 21.1

5. Assisted Reproductive Technologies ARTs are methods that replace the source of a male or female gamete, aid fertilization or provide a uterus Developed to treat infertility but are becoming part of genetic screening The US Government does not regulate ARTs - However, the British Government does

6. Infertility and Subfertility Infertility is the inability to conceive a child after a year of frequent intercourse without contraceptives Subfertility distinguishes couples who can conceive, but require longer time than usual Affect one in six couples A physical cause can be identified in 90% of cases: 30% in males, 60% in females

7. One in 25 men are infertile Easier to detect, but often harder to treat than female infertility Most cases of male infertility are genetic Causes of infertility include: - Low sperm count (oligospermia) - A malfunctioning immune system - A varicose vein in the scrotum - Structural sperm defects Male Infertility

8. Male Infertility Box Figure 1

9. Most cases of male infertility are genetic - Due to small deletions of Y chromosome that remove genes important for spermatogenesis - Mutations in genes for androgen receptors or other hormones promoting sperm development In cases of low sperm count, sperm can be stored frozen, then pooled Lack of motility in sperm prevents movement in the female reproductive tract

10. Many women with subfertility or infertility have irregular menstrual cycles - This makes it difficult to pinpoint when conception is most likely Tracking ovulation cycles aids in determination of the most likely days for conception Abnormalities in any part of the female reproductive system can cause infertility Female Infertility

11. Figure 21.2

12. Fertility drugs stimulate ovulation but may induce release of multiple oocytes Blocked fallopian tubes can result in ectopic pregnancy (tubal pregnancy). Excess tissue growth in uterine lining may make it inhospitable for an embryo - Fibroids: benign tumors - Endometriosis: buildup of uterine lining Female Infertility

13. Secretions in the vagina and cervix may be hostile to sperm Infertility may also result if the oocyte fails to release sperm-attracting chemicals Early pregnancy loss due to an abnormal chromosome number is more common in older females - May appear as infertility because bleeding resembles a heavy menstrual flow Female Infertility

14. The man is checked first, because it is easier, less costly and less painful to obtain sperm than oocytes - Sperm are checked for number (sperm count) motility and morphology (shape) A gynecologist can then check the female to see if reproductive organs are present and functioning Psychological factors may also be at play Infertility Tests

15. Assisted Reproductive Technologies (ARTs) Many people with fertility problems use alternative ways to conceive In the US, about 1% of the 4 million births each year are from ARTs Several of the ARTs were developed in nonhuman animals

16. Assisted Reproductive Technologies (ARTs) Examples - Intrauterine insemination - Surrogate motherhood - In vitro fertilization (IVF) - Gamete intrafallopian transfer (GIFT) - Zygote intrafallopian transfer (ZIFT) - Oocyte banking and donation - Preimplantation genetic diagnosis

19. Intrauterine Insemination Donated sperm is placed in a woman’s reproductive tract, typically at the cervix or in uterus Success rate is 5-15% 1790: first reported pregnancy from artificial insemination 1953: methods for freezing and storing sperm were developed Sperm catalogs list personal characteristics

20. Surrogate Motherhood In surrogate motherhood, a woman carries a pregnancy to term for another woman who cannot conceive and/or carry the pregnancy Custody rights are given up at birth A surrogate mother may or may not have contributed an oocyte Complex legal and emotional issues must be considered

21. In vitro Fertilization (IVF) For in vitro fertilization, a sperm fertilizes an oocyte in a culture dish Embryos are transferred to the oocyte donor’s uterus (or a surrogate’s uterus) for implantation 1978: First IVF child born (Louise Joy Brown) - Since then, 4 million IVF children Intracytoplasmic sperm injection (ICSI) is more effective than IVF alone

22. Intracytoplasmic Sperm Injection For cases in which sperm cannot penetrate the oocyte, IVF can be accompanied by ICSI which injects sperm directly into the oocyte ICSI allows conception in cases of low sperm count, abnormal sperm shape, sperm motility problems, - And in cases where male has spinal cord injuries and cannot ejaculate

23. Intracytoplasmic Sperm Injection Figure 21.3

24. Gamete Intrafallopian Transfer (GIFT) GIFT is a method in which superovulated oocytes from a woman and sperm from her partner are placed together in her uterine (fallopian) tube Fertilization occurs in the woman’s body Allows conception in cases of fallopian tube blockage 22% success rate and costs less than IVF

25. Zygote Intrafallopian Transfer (ZIFT) IVF ovum is introduced into the uterine tube and allowed to move to the uterus for implantation Also about 22% successful GIFT and ZIFT are done much less frequently than IVF - They often will not work for women with scarred uterine tubes

26. Oocyte Banking and Donation Oocytes, like sperm, can be stored frozen Only 3% successful New technique can freeze strips of ovarian tissue Difficulties because oocytes pause in meiosis II until fertilization occurs Women can store their own oocytes to have children later or prior to undergoing chemotherapy Donated oocytes can be used by women with infertility problems; 28-50% successful Embryo adoption is a variation on oocyte donation

27. Preimplantation Genetic Diagnosis (PGD) This PGD technique allows detection of genetic and chromosomal abnormalities prior to implantation One cell or blastomere of an 8-celled embryo can be removed for testing - The remaining cells will complete normal development About 29% success rate

28. Preimplantation Genetic Diagnosis (PGD) 1989: First children who had PGD - Used to select females who could not inherit X-linked disease from mother 1992: First child born following PGD to screen for cystic fibrosis allele present in her family PGD can be combined with IVF for women who have had multiple miscarriages

29. Preimplantation Genetic Diagnosis (PGD) Figure 21.4

30. Table 21.1

31. Extra Embryos Sometimes ARTs leave “extra” oocytes, fertilized ova, or very early embryos

32. Using Extra Embryos Figure 21.5

33. Extra Embryos A similar case to the Lyons’ involved a California woman named Nadya Suleman - She had eight fertilized ova left over after using six to produce her six young children - She did not want to destroy these ova or continue to store them - She was implanted with them, and in early 2009 gave birth to octuplets!

34. Polar Body Biopsy An experimental ART that increases the success of IVF Based on Mendel’s first law (segregation of alleles) Enables physicians to perform genetic tests on polar bodies and infer the genotype of the accompanying oocyte Oocytes that pass this test can be fertilized in vitro and the resulting embryo implanted

35. Polar Body Biopsy Figure 21.6

36. Assisted Reproductive Disasters ARTs introduce ownership and parentage issues Another controversy is that human genome information is providing more traits to track and perhaps control in coming generations - So, who will decide which traits are worth living with, and which are not?

37. Table 21.3 Table 21.4