1 00:00:06,645 --> 00:00:09,047 In 1978, Louise Brown became 2 00:00:09,047 --> 00:00:14,450 the world's first baby to be born by in vitro fertilization, or IVF. 3 00:00:14,450 --> 00:00:17,780 Her birth revolutionized the field of reproductive medicine. 4 00:00:17,780 --> 00:00:20,931 Given that approximately one in eight heterosexual couples 5 00:00:20,931 --> 00:00:22,997 has difficulty conceiving, 6 00:00:22,997 --> 00:00:25,172 and that homosexual couples and single parents 7 00:00:25,172 --> 00:00:27,804 often need clinical help to make a baby, 8 00:00:27,804 --> 00:00:30,561 the demand for IVF has been growing. 9 00:00:30,561 --> 00:00:36,889 IVF is so common, that more than 5 million babies have been born through this technology. 10 00:00:36,889 --> 00:00:42,645 IVF works by mimicking the brilliant design of sexual reproduction. 11 00:00:42,645 --> 00:00:44,789 In order to understand IVF, 12 00:00:44,789 --> 00:00:49,516 we first need to take a look at the natural process of baby making. 13 00:00:49,516 --> 00:00:53,788 Believe it or not, it all starts in the brain. 14 00:00:53,788 --> 00:00:57,127 Roughly fifteen days before fertilization can happen, 15 00:00:57,127 --> 00:01:02,612 the anterior pituitary gland secretes follicle stimulating hormone, FSH, 16 00:01:02,612 --> 00:01:05,476 which ripens a handful of follicles of the ovary 17 00:01:05,476 --> 00:01:07,817 that then release estrogen. 18 00:01:07,817 --> 00:01:09,788 Each follicle contains one egg, 19 00:01:09,788 --> 00:01:14,340 and on average, only one follicle becomes fully mature. 20 00:01:14,340 --> 00:01:17,295 As it grows and continues to release estrogen, 21 00:01:17,295 --> 00:01:21,664 this hormone not only helps coordinate growth and preparation of the uterus, 22 00:01:21,664 --> 00:01:27,088 it also communicates to the brain how well the follicle is developing. 23 00:01:27,088 --> 00:01:29,466 When the estrogen level is high enough, 24 00:01:29,466 --> 00:01:35,378 the anterior pituitary releases a surge of luteinizing hormone, LH, 25 00:01:35,378 --> 00:01:37,213 which triggers ovulation 26 00:01:37,213 --> 00:01:42,417 and causes the follicle to rupture and release the egg. 27 00:01:42,417 --> 00:01:44,468 Once the egg leaves the ovary, 28 00:01:44,468 --> 00:01:49,179 it is directed into the Fallopian tube by the finger-like fimbriae. 29 00:01:49,179 --> 00:01:52,681 If the egg is not fertilized by sperm within 24 hours, 30 00:01:52,681 --> 00:01:54,807 the unfertilized egg will die, 31 00:01:54,807 --> 00:01:57,266 and the entire system will reset itself, 32 00:01:57,266 --> 00:02:02,087 preparing to create a new egg and uterine lining the following month. 33 00:02:02,087 --> 00:02:05,011 The egg is the largest cell in the body 34 00:02:05,011 --> 00:02:08,473 and is protected by a thick, extracellular shell of sugar 35 00:02:08,473 --> 00:02:12,325 and protein called the zona pellucida. 36 00:02:12,325 --> 00:02:16,576 The zona thwarts the entry and fusion of more than one sperm, 37 00:02:16,576 --> 00:02:19,978 the smallest cell in the body. 38 00:02:19,978 --> 00:02:23,060 It takes a man two to three months to make sperm, 39 00:02:23,060 --> 00:02:26,220 and the process constantly renews. 40 00:02:26,220 --> 00:02:31,856 Each ejaculation during sexual intercourse releases more than 100 million sperm. 41 00:02:31,856 --> 00:02:37,035 But only 100 or so will ultimately make it to the proximity of the egg, 42 00:02:37,035 --> 00:02:43,232 and only one will successfully penetrate through the armor of the zona pellucida. 43 00:02:43,232 --> 00:02:45,514 Upon successful fertilization, 44 00:02:45,514 --> 00:02:48,756 the zygote immediately begins developing into an embryo, 45 00:02:48,756 --> 00:02:52,006 and takes about three days to reach the uterus. 46 00:02:52,006 --> 00:02:54,282 There, it requires another three or so days 47 00:02:54,282 --> 00:02:59,742 to implant firmly into the endometrium, the inner lining of the uterus. 48 00:02:59,742 --> 00:03:02,895 Once implanted, the cells that are to become the placenta 49 00:03:02,895 --> 00:03:06,037 secrete a hormone that signals to the ovulated follicle 50 00:03:06,037 --> 00:03:08,898 that there is a pregnancy in the uterus. 51 00:03:08,898 --> 00:03:12,403 This helps rescue that follicle, now called the corpus luteum, 52 00:03:12,403 --> 00:03:17,697 from degenerating as it normally would do in that stage of the menstrual cycle. 53 00:03:17,697 --> 00:03:20,839 The corpus luteum is responsible for producing the progesterone 54 00:03:20,839 --> 00:03:25,594 required to maintain the pregnancy until six to seven weeks of gestation, 55 00:03:25,594 --> 00:03:28,273 when the placenta develops and takes over, 56 00:03:28,273 --> 00:03:32,213 until the baby is born approximately 40 weeks later. 57 00:03:32,213 --> 00:03:35,587 Now, how do you make a baby in a lab? 58 00:03:35,587 --> 00:03:37,926 In patients undergoing IVF, 59 00:03:37,926 --> 00:03:42,333 FSH is administered at levels that are higher than naturally occuring 60 00:03:42,333 --> 00:03:45,859 to cause a controlled overstimulation of the ovaries 61 00:03:45,859 --> 00:03:49,599 so that they ultimately produce multiple eggs. 62 00:03:49,599 --> 00:03:53,462 The eggs are then retrieved just before ovulation would occur, 63 00:03:53,462 --> 00:03:55,738 while the woman is under anesthesia, 64 00:03:55,738 --> 00:04:00,111 through an aspirating needle that is guided by ultrasound. 65 00:04:00,111 --> 00:04:05,029 Most sperm samples are produced by masturbation. 66 00:04:05,029 --> 00:04:09,599 In the laboratory, the identified eggs are stripped of surrounding cells 67 00:04:09,599 --> 00:04:13,594 and prepared for fertilization in a petri dish. 68 00:04:13,594 --> 00:04:16,851 Fertilization can occur by one of two techniques. 69 00:04:16,851 --> 00:04:20,307 In the first, the eggs are incubated with thousands of sperm 70 00:04:20,307 --> 00:04:24,725 and fertilization occurs naturally over a few hours. 71 00:04:24,725 --> 00:04:27,835 The second technique maximizes certainty of fertilization 72 00:04:27,835 --> 00:04:32,465 by using a needle to place a single sperm inside the egg. 73 00:04:32,465 --> 00:04:37,181 This is particularly useful when there is a problem with the quality of the sperm. 74 00:04:37,181 --> 00:04:41,819 After fertilization, embryos can be further screened for genetic suitability, 75 00:04:41,819 --> 00:04:44,480 frozen for later attempted pregnancies, 76 00:04:44,480 --> 00:04:48,687 or delivered into the woman's uterus via catheter. 77 00:04:48,687 --> 00:04:53,913 Common convention is to transfer the embryo three days after fertilization, 78 00:04:53,913 --> 00:04:56,542 when the embryo has eight cells, 79 00:04:56,542 --> 00:05:01,137 or on day five, when the embryo is called a blastocyst, 80 00:05:01,137 --> 00:05:03,769 and has hundreds of cells. 81 00:05:03,769 --> 00:05:08,717 If the woman's eggs are of poor quality due to age or toxic exposures, 82 00:05:08,717 --> 00:05:11,478 or have been removed due to cancer, 83 00:05:11,478 --> 00:05:14,237 donor eggs may be used. 84 00:05:14,237 --> 00:05:18,671 In the case that the intended mother has a problematic uterus, or lacks one, 85 00:05:18,671 --> 00:05:22,622 another woman, called the gestational carrier or surrogate, 86 00:05:22,622 --> 00:05:26,448 can use her uterus to carry the pregnancy. 87 00:05:26,448 --> 00:05:28,378 To increase the odds of success, 88 00:05:28,378 --> 00:05:32,330 which are as high as 40% for a woman younger than 35, 89 00:05:32,330 --> 00:05:36,536 doctors sometimes transfer multiple embryos at once, 90 00:05:36,536 --> 00:05:39,512 which is why IVF results in twins and triplets 91 00:05:39,512 --> 00:05:43,050 more often than natural pregnancies. 92 00:05:43,050 --> 00:05:48,003 However, most clinics seek to minimize the chances of multiple pregnancies, 93 00:05:48,003 --> 00:05:51,726 as they are riskier for mothers and babies. 94 00:05:51,726 --> 00:05:56,336 Millions of babies, like Louise Brown, have been born from IVF 95 00:05:56,336 --> 00:05:59,501 and have had normal, healthy lives. 96 00:05:59,501 --> 00:06:02,728 The long-term health consequences of ovarian stimulation 97 00:06:02,728 --> 00:06:05,879 with IVF medicines are less clear, 98 00:06:05,879 --> 00:06:09,920 though so far, IVF seems safe for women. 99 00:06:09,920 --> 00:06:11,876 Because of better genetic testing, 100 00:06:11,876 --> 00:06:13,714 delayed childbearing, 101 00:06:13,714 --> 00:06:16,765 increased accessibility and diminishing cost, 102 00:06:16,765 --> 00:06:22,582 it's not inconceivable that artificial baby making via IVF and related techniques 103 00:06:22,582 --> 00:06:26,717 could outpace natural reproduction in years to come.